CDH1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCDH1, Arc-1, CD324, CDHE, ECAD, LCAM, UVO, cadherin 1, BCDS1, E-cadherin, uvomorulin
External IDsOMIM: 192090 MGI: 88354 HomoloGene: 20917 GeneCards: CDH1
Orthologs
SpeciesHumanMouse
Entrez

999

12550

Ensembl

ENSG00000039068

ENSMUSG00000000303

UniProt

P12830

P09803

RefSeq (mRNA)

NM_004360
NM_001317184
NM_001317185
NM_001317186

NM_009864

RefSeq (protein)

NP_001304113
NP_001304114
NP_001304115
NP_004351

NP_033994

Location (UCSC)Chr 16: 68.74 – 68.84 MbChr 8: 107.33 – 107.4 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Cadherin-1 or Epithelial cadherin (E-cadherin), (not to be confused with the APC/C activator protein CDH1) is a protein that in humans is encoded by the CDH1 gene.[5] Mutations are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. CDH1 has also been designated as CD324 (cluster of differentiation 324). It is a tumor suppressor gene.[6][7]

History

The discovery of cadherin cell-cell adhesion proteins is attributed to Masatoshi Takeichi, whose experience with adhering epithelial cells began in 1966.[8] His work originally began by studying lens differentiation in chicken embryos at Nagoya University, where he explored how retinal cells regulate lens fiber differentiation. To do this, Takeichi initially collected media that had previously cultured neural retina cells (CM) and suspended lens epithelial cells in it. He observed that cells suspended in the CM media had delayed attachment compared to cells in his regular medium. His interest in cell adherence was sparked, and he moved on to examine attachment in other conditions such as in the presence of protein, magnesium, and calcium. At this point in 1970s, little was understood about the specific roles these ions played.[9] Therefore, Takeichi’s work in discovering calcium’s role in cell-cell adhesion was highly transformative.[10][11]

Takeichi went on to discover the existence of multiple cadherins, beginning with E-cadherin. Using rats immunized with F9 cells, he worked with an undergraduate student in the Okada laboratory, Noboru Suzuki, to generate mouse antibodies called ECCD1. This antibody blocked cell-adhesion ability and showed a calcium-dependent interaction with its antigen, E-cadherin.[12] They went on to find that ECCD1 reacted to a variety of epithelial cells when comparing antibody distributions.[13] The delay Takeichi experienced in specifically discovering Ecadherin was most likely due to the model he used to initially investigate cell adherence. The chinese hamster V79 cells apparently did not express E-cadherin, but instead 20 other subtypes that have since been discovered.[14]

Function

Cadherin-1 is a classical member of the cadherin superfamily. The encoded protein is a calcium-dependent cell–cell adhesion glycoprotein composed of five extracellular cadherin repeats, a transmembrane region, and a highly conserved cytoplasmic tail. Mutations in this gene are correlated with gastric, breast, colorectal, thyroid, and ovarian cancers. Loss of function is thought to contribute to progression in cancer by increasing proliferation, invasion, and/or metastasis. The ectodomain of this protein mediates bacterial adhesion to mammalian cells, and the cytoplasmic domain is required for internalization. Identified transcript variants arise from mutation at consensus splice sites.[15]

E-cadherin (epithelial) is the most well-studied member of the cadherin family and is an essential transmembrane protein within adherens junctions. In addition to E-cadherin, adherens junctions are composed of the intracellular components, p120-catenin, beta-catenin, and alpha-catenin.[16] Together, these proteins stabilize epithelial tissues and regulate intercellular exchange. The structure of E-cadherin consists of 5 cadherin repeats (EC1 ~ EC5) in the extracellular domain, one transmembrane domain, and a highly-phosphorylated intracellular domain. This region is vital to beta-catenin binding and, therefore, to E-cadherin function.[17] Beta-catenin can also bind to alpha-catenin. Alpha-catenin participates in regulation of actin-containing cytoskeletal filaments. In epithelial cells, E-cadherin-containing cell-to-cell junctions are often adjacent to actin-containing filaments of the cytoskeleton.

E-cadherin is first expressed in the 2-cell stage of mammalian development, and becomes phosphorylated by the 8-cell stage, where it causes compaction.[18] In adult tissues, E-cadherin is expressed in epithelial tissues, where it is constantly regenerated with a 5-hour half-life on the cell surface. Cell–cell interactions mediated by E-cadherin are crucial to blastula formation in many animals.[19]

Neighboring epithelial cells can transduce mechanical information via E-cadherin interactions, here depicted as a generic cadherin, Actin filaments are associated with several adherens complex proteins, such as α-catenin and vinculin. The activity of these proteins and E-cadherin allows for tensile stimulus to be exerted one from actomyosin system to another, permitting tissue coordination.

Cell cycle

E-cadherin has been known to mediate adhesion-dependent proliferation inhibition by triggering cell cycle exit via contact inhibition of proliferation (CIP) and recruitment of the Hippo pathway.[20] E-cadherin adhesions inhibit growth signals, which initiates a kinase cascade that excludes the transcription factor YAP from the nucleus. Conversely, decreasing cell density (decreasing cell-cell adhesion) or applying mechanical stretch to place E-cadherins under increased tension promotes cell cycle entry and YAP nuclear localization.[21]

Cell sorting during epithelial budding

E-cadherin has been found to have a role in epithelial morphogenesis and branching, such as during the formation of epithelial buds. Physiologically, branching is an important feature that allows tissues, such as salivary glands and pancreatic buds, to maximize functional surface areas.[22] It has been discovered that the application of appropriate growth factors and extracellular matrix can induce branching in tissue, but the mechanisms of branching appear to differ between single-layered and stratified epithelium.[23][24]

Single-layered branching occurs as nearby mechanical influences, such as airway smooth muscle cells, cause epithelial sheets buckle.[25] Stratified epithelial cannot respond to stimulus in the same way due to the absence of internal space (i.e. lumen) that allows tissue sheet flexibility.[26] Instead, it appears stratified epithelial buds are generated by the clefting of one original epithelial cell cluster. Investigations in salivary glands revealed that buds expand as new cells are uniformly distributed across the peripheral surface. Surface-derived cells continue to replicate and produce daughter cells, which then move from the interior back to the surface. This movement is maintained by an E-cadherin gradient, in which surface cells have low levels of E-cadherin and interior cells have high levels of E-cadherin. Such a system allows for increased interactions between interior cells, limiting mobility and ensuring they remain more static, while likewise ensuring the surface cells are comparatively less hindered. This gives a fluidity to their movement within the stratified epithelia, until they begin to accumulate at the edges of the forming bud.[27]

While this gradient is important for cell sorting within the tissue layers, additional experiments show that the physical generation of buds is dependent on cell-matrix interactions[13]. As low-E-cadherin cells accumulate at the surface, they tightly adhere to the basement membrane, allowing the epithelia to cleft and bud as the surface area expands and folds. If the structure of the basement membrane is disrupted, such as by collagenase, the low-E-cadherin cells no longer have a barrier to interact with. Surface-derived daughter cells fail to remain at the periphery to initiate budding under these conditions, yet budding can be reestablished with basement membrane restoration.

Cell sorting during gastrulation

The adhesive qualities of E-cadherin indicate it could be a relevant player within germ-layer organization during gastrulation. Gastrulation is a fundamental phase of vertebrate development in which three primary germ layers are defined, ectoderm, mesoderm, and endoderm.[28] Cell adhesion has been linked to progenitor sorting, where ectoderm was found to be the least cohesive and mesoderm was comparable to endoderm cohesion.[29] Initial work depleting calcium from media and, more strikingly, the impairment of E-cadherin both greatly impaired primary germ layer cohesion. As cohesive properties of progenitors were further examined, higher concentrations of CDH-1 were found on mesoderm or endoderm than on ectoderm. While adhesion is a factor in gastrulation, the driving factor in cell sorting was instead found to be in cell-cortex tension[15]. Disrupting the actomyosin-dependent cell cortex with actin depolymerizers and myosin-II inhibitors interrupted impeded tension balances and was sufficient to inhibit cell sorting. This is likely because cell sorting is driven by energy minimization. WIthin tissue energetics, tension plays an important role in ensuring: (1) lower surface tension surrounds the higher surface tension germ layers; (2) aggregate surface tension is appropriately increased; and (3) tension is higher at the cell-to-medium interface than cell-to-cell interface[8]. Cellular adhesion must still be considered for a complete understanding of progenitor sorting, as it directly  diminishes the energetic effects of tension. Combined, tension and adhesion increase aggregate surface tension, which allows for unique interactions between differing germ layers and appropriate cell sorting.[30]

Cell migration

Cell migration is vital for constructing and maintaining multicellular organization. Morphogenesis involves numerous events of cell migration, such as the migration of epithelial sheets in gastrulation, the neural crest cell migration, or posterior lateral line primordium migration.[31] It is known that cells that begin to internalize at the dorsal surface of the embryo mobilize to extend the axis and direct posterior prechordal plate and notochord precursors. How cells are able to orient themselves during this process is dependent on the protrusions of “follower cells” to guide the leading cells in the appropriate direction.[32]

E-cadherin has an active role in collective cell dynamics, such as by directing the migration of mesendoderm towards the animal pole.[33] It has been demonstrated that the genetic knockdown of E-cadherin results in random orientations of the cellular protrusions, resulting in cellular migration that is random and no longer unified.[34] Knockdowns in leading and following cell groups both resulted in a loss of orientation, which could be rescued by re-expressing E-cadherin. The information E-cadherin transmitted from cell to cell was directional information inherent to cytoskeletal tension. Restoring only the external adhesion capability of E-cadherin was not enough to rescue protrusion orientation during knockdown experiments. The intracellular domain of E-cadherin is essential due to its mechanotransduction characteristics; it interacts with alpha-catenin and vinculin and altogether allows for the mechanosensation of tension.[35][36][37] The exact mechanism on how mechanosensation directs actin-rich protrusions is yet to be elucidated, however initial investigations suggest regulation of PI3K activity is involved.[38]

Force transduction by E-cadherin

Adherens junctions (AJs) form homotypic dimers between neighboring cells, where the intracellular protein complex interacts with the actomyosin cytoskeleton. p120-catenin controls E-cadherin membrane localization, while β-catenin and α-catenin provide the link that connect AJs to the cytoskeleton. If AJs experience tensile force when β-catenin is bound, the interaction, known as a catch bond interaction, between α-catenin and F-actin is reinforced. This exposes the a previously inaccessible actin binding site within α-catenin.[39] The binding of vinculin to α-catenin offers the protein complex another linkage with actin in addition to recruiting proteins such as Mena/VASP.[40]

Coordination of the actomyosin network between neighboring cells permits collective cellular activity, such as contractility during morphogenesis. This network is better equipped to maintain tissue integrity if under intercellular stress, but should not be considered a static system. E-cadherin is involved in cellular responses and transcriptional activators that impact migration, growth, and reorganization.[41][42]

Mechanism of action

E-cadherin interacts with its environment through numerous pathways. One mechanism that it is involved in is the migration of tissue sheets via cryptic lamellipodia. Rac1 and its effectors act at the front edge of this structure to initiate actin polymerization, allowing the cell to generate force at the cellular margin and forward movement.[43] As leader cells extend their lamellipodia, followers also extend protrusions to collect information on where the tissue sheet it moving. Cell migration is dependent on the generation of a polarized state, with Rac1 at the front and Rho-mediated adhesion at the rear. The release of Merlin from cell contacts partially mediates concomitant migration by acting as a mechanochemical transducer.[44] This tumour suppressor protein relocalizes from cortical cell-cell junctions to the cytoplasm during migration to coordinate Rac1 activation. Other pathways can then modulate Merlin activity, such as circumferential actin belts, which suppresses the nuclear export of Merlin and its interaction with E-cadherin.[45]

Interactions

CDH1 (gene) has been shown to interact with

Clinical significance

Immunohistochemistry for E-cadherin in invasive lobular carcinoma, showing loss of expression in invasive tumor cells (white arrow).

Loss of E-cadherin function or expression has been implicated in cancer progression and metastasis.[63][64] E-cadherin downregulation decreases the strength of cellular adhesion within a tissue, resulting in an increase in cellular motility. This in turn may allow cancer cells to cross the basement membrane and invade surrounding tissues.[64] E-cadherin is also used by pathologists to diagnose different kinds of breast cancer. When compared with invasive ductal carcinoma, E-cadherin expression is markedly reduced or absent in the great majority of invasive lobular carcinomas when studied by immunohistochemistry.[65] E-cadherin and N-cadherin temporal-spatial expression are tightly regulated during cranial suture fusion in craniofacial development.[66]


Cancer

Metastasis

Transitions between epithelial and mesenchymal states play important roles in embryonic development and cancer metastasis. E-cadherin level changes in EMT (epithelial-mesenchymal transition) and MET (mesenchymal-epithelial transition). E-cadherin acts as an invasion suppressor and a classical tumor suppressor gene in pre-invasive lobular breast carcinoma.[67]

EMT

E-cadherin is a crucial type of cell–cell adhesion to hold the epithelial cells tight together. E-cadherin can sequester β-catenin on the cell membrane by the cytoplasmic tail of E-cadherin. Loss of E-cadherin expression results in releasing β-catenin into the cytoplasm. Liberated β-catenin molecules may migrate into the nucleus and trigger the expression of EMT-inducing transcription factors. Together with other mechanisms, such as constitutive RTK activation, E-cadherin loss can lead cancer cells to the mesenchymal state and undergo metastasis. E-cadherin is an important switch in EMT.[67]

MET

The mesenchymal state cancer cells migrate to new sites and may undergo METs in certain favorable microenvironment. For example, the cancer cells can recognize differentiated epithelial cell features in the new sites and upregulate E-cadherin expression. Those cancer cells can form cell–cell adhesions again and return to an epithelial state.[67]

Examples

  • Inherited inactivating mutations in CDH1 are associated with hereditary diffuse gastric cancer. Individuals with this condition have up to a 70% lifetime risk of developing diffuse gastric carcinoma, and females with CDH1 mutations have up to a 60% lifetime risk of developing lobular breast cancer.[68]
  • Inactivation of CDH1 (accompanied with loss of the wild-type allele) in 56% of lobular breast carcinomas.[69][70]
  • Inactivation of CDH1 in 50% of diffuse gastric carcinomas.[71]
  • Complete loss of E-cadherin protein expression in 84% of lobular breast carcinomas.[72]

Genetic and epigenetic control

Several proteins such as SNAI1,[73][74] ZEB2,[75] SNAI2,[76][77] TWIST1[78] and ZEB1[79] have been found to downregulate E-cadherin expression. When expression of those transcription factors is altered, transcriptional repressors of E-cadherin were overexpressed in tumor cells. Another group of genes, such as AML1, p300 and HNF3,[80] can upregulate the expression of E-cadherin.[81]

In order to study the epigenetic regulation of E-cadherin, M Lombaerts et al. performed a genome wide expression study on 27 human mammary cell lines. Their results revealed two main clusters that have the fibroblastic or epithelial phenotype, respectively. In close examination, the clusters showing fibroblast phenotypes only have either partial or complete CDH1 promoter methylation, while the clusters with epithelial phenotypes have both wild-type cell lines and cell lines with mutant CDH1 status. The authors also found that EMT can happen in breast cancer cell lines with hypermethylation of CDH1 promoter, but in breast cancer cell lines with a CDH1 mutational inactivation EMT cannot happen. It contradicts the hypothesis that E-cadherin loss is the initial or primary cause for EMT. In conclusion, the results suggest that “E-cadherin transcriptional inactivation is an epi-phenomenon and part of an entire program, with much more severe effects than loss of E-cadherin expression alone”.[81]

Other studies also show that epigenetic regulation of E-cadherin expression occurs during metastasis. The methylation patterns of the E-cadherin 5’ CpG island are not stable. During metastatic progression of many cases of epithelial tumors, a transient loss of E-cadherin is seen and the heterogeneous loss of E-cadherin expression results from a heterogeneous pattern of promoter region methylation of E-cadherin.[82]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000039068 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000000303 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Huntsman DG, Caldas C (Mar 1999). "Assignment1 of the E-cadherin gene (CDH1) to chromosome 16q22.1 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 83 (1–2): 82–83. doi:10.1159/000015134. PMID 9925936. S2CID 39971762.
  6. Semb H, Christofori G (December 1998). "The tumor-suppressor function of E-cadherin". American Journal of Human Genetics. 63 (6): 1588–1593. doi:10.1086/302173. PMC 1377629. PMID 9837810.
  7. Wong AS, Gumbiner BM (June 2003). "Adhesion-independent mechanism for suppression of tumor cell invasion by E-cadherin". The Journal of Cell Biology. 161 (6): 1191–1203. doi:10.1083/jcb.200212033. PMC 2173007. PMID 12810698.
  8. Takeichi M (January 2018). "Historical review of the discovery of cadherin, in memory of Tokindo Okada". Development, Growth & Differentiation. 60 (1): 3–13. doi:10.1111/dgd.12416. PMID 29278270. S2CID 20240634.
  9. Takeichi M, Ozaki HS, Tokunaga K, Okada TS (May 1979). "Experimental manipulation of cell surface to affect cellular recognition mechanisms". Developmental Biology. 70 (1): 195–205. doi:10.1016/0012-1606(79)90016-2. PMID 456740.
  10. Urushihara H, Ozaki HS, Takeichi M (May 1979). "Immunological detection of cell surface components related with aggregation of Chinese hamster and chick embryonic cells". Developmental Biology. 70 (1): 206–216. doi:10.1016/0012-1606(79)90017-4. PMID 110634.
  11. Urushihara H, Takeichi M (June 1980). "Cell-cell adhesion molecule: identification of a glycoprotein relevant to the Ca2+-independent aggregation of Chinese hamster fibroblasts". Cell. 20 (2): 363–371. doi:10.1016/0092-8674(80)90622-4. PMID 7388946. S2CID 39836422.
  12. Yoshida-Noro C, Suzuki N, Takeichi M (January 1984). "Molecular nature of the calcium-dependent cell-cell adhesion system in mouse teratocarcinoma and embryonic cells studied with a monoclonal antibody". Developmental Biology. 101 (1): 19–27. doi:10.1016/0012-1606(84)90112-X. PMID 6692973.
  13. Lampugnani MG, Resnati M, Raiteri M, Pigott R, Pisacane A, Houen G, et al. (September 1992). "A novel endothelial-specific membrane protein is a marker of cell-cell contacts". The Journal of Cell Biology. 118 (6): 1511–1522. doi:10.1083/jcb.118.6.1511. PMC 2289607. PMID 1522121.
  14. Takeichi M (November 1977). "Functional correlation between cell adhesive properties and some cell surface proteins". The Journal of Cell Biology. 75 (2 Pt 1): 464–474. doi:10.1083/jcb.75.2.464. PMC 2109947. PMID 264120.
  15. "Entrez Gene: CDH1 cadherin 1, type 1, E-cadherin (epithelial)".
  16. Hartsock A, Nelson WJ (March 2008). "Adherens and tight junctions: structure, function and connections to the actin cytoskeleton". Biochimica et Biophysica Acta (BBA) - Biomembranes. Apical Junctional Complexes Part I. 1778 (3): 660–669. doi:10.1016/j.bbamem.2007.07.012. PMC 2682436. PMID 17854762.
  17. Faux MC, Coates JL, Kershaw NJ, Layton MJ, Burgess AW (November 2010). "Independent interactions of phosphorylated β-catenin with E-cadherin at cell-cell contacts and APC at cell protrusions". PLOS ONE. 5 (11): e14127. Bibcode:2010PLoSO...514127F. doi:10.1371/journal.pone.0014127. PMC 2994709. PMID 21152425.
  18. Hyafil F, Babinet C, Jacob F (1981). "Cell-cell interactions in early embryogenesis: a molecular approach to the role of calcium". Cell. 26 (3 Pt 1): 447–454. doi:10.1016/0092-8674(81)90214-2. PMID 6976838. S2CID 40534936.
  19. Fleming TP, Papenbrock T, Fesenko I, Hausen P, Sheth B (August 2000). "Assembly of tight junctions during early vertebrate development". Seminars in Cell & Developmental Biology. 11 (4): 291–299. doi:10.1006/scdb.2000.0179. PMID 10966863.
  20. McClatchey AI, Yap AS (October 2012). "Contact inhibition (of proliferation) redux". Current Opinion in Cell Biology. Cell-to-cell contact and extracellular matrix. 24 (5): 685–694. doi:10.1016/j.ceb.2012.06.009. PMID 22835462.
  21. Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, et al. (March 2011). "Yap1 acts downstream of α-catenin to control epidermal proliferation". Cell. 144 (5): 782–795. doi:10.1016/j.cell.2011.02.031. PMC 3237196. PMID 21376238.
  22. Wang S, Sekiguchi R, Daley WP, Yamada KM (March 2017). "Patterned cell and matrix dynamics in branching morphogenesis". The Journal of Cell Biology. 216 (3): 559–570. doi:10.1083/jcb.201610048. PMC 5350520. PMID 28174204.
  23. Nogawa H, Ito T (April 1995). "Branching morphogenesis of embryonic mouse lung epithelium in mesenchyme-free culture". Development. 121 (4): 1015–1022. doi:10.1242/dev.121.4.1015. PMID 7538066.
  24. Ewald AJ, Brenot A, Duong M, Chan BS, Werb Z (April 2008). "Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis". Developmental Cell. 14 (4): 570–581. doi:10.1016/j.devcel.2008.03.003. PMC 2773823. PMID 18410732.
  25. Kim HY, Pang MF, Varner VD, Kojima L, Miller E, Radisky DC, Nelson CM (September 2015). "Localized Smooth Muscle Differentiation Is Essential for Epithelial Bifurcation during Branching Morphogenesis of the Mammalian Lung". Developmental Cell. 34 (6): 719–726. doi:10.1016/j.devcel.2015.08.012. PMC 4589145. PMID 26387457.
  26. Nelson CM (February 2016). "On Buckling Morphogenesis". Journal of Biomechanical Engineering. 138 (2): 021005. doi:10.1115/1.4032128. PMC 4844087. PMID 26632268.
  27. Wang S, Matsumoto K, Lish SR, Cartagena-Rivera AX, Yamada KM (July 2021). "Budding epithelial morphogenesis driven by cell-matrix versus cell-cell adhesion". Cell. 184 (14): 3702–3716.e30. doi:10.1016/j.cell.2021.05.015. PMC 8287763. PMID 34133940.
  28. Shimizu T, Yabe T, Muraoka O, Yonemura S, Aramaki S, Hatta K, et al. (June 2005). "E-cadherin is required for gastrulation cell movements in zebrafish". Mechanisms of Development. 122 (6): 747–763. doi:10.1016/j.mod.2005.03.008. PMID 15905076. S2CID 16117456.
  29. Krieg M, Arboleda-Estudillo Y, Puech PH, Käfer J, Graner F, Müller DJ, Heisenberg CP (April 2008). "Tensile forces govern germ-layer organization in zebrafish". Nature Cell Biology. 10 (4): 429–436. doi:10.1038/ncb1705. PMID 18364700. S2CID 22340931.
  30. Lecuit T, Lenne PF (August 2007). "Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis". Nature Reviews. Molecular Cell Biology. 8 (8): 633–644. doi:10.1038/nrm2222. PMID 17643125. S2CID 1376635.
  31. Olson HM, Nechiporuk AV (2018). "Using Zebrafish to Study Collective Cell Migration in Development and Disease". Frontiers in Cell and Developmental Biology. 6: 83. doi:10.3389/fcell.2018.00083. PMC 6107837. PMID 30175096.
  32. Boutillon A, Escot S, Elouin A, Jahn D, González-Tirado S, Starruß J, et al. (June 2022). "Guidance by followers ensures long-range coordination of cell migration through α-catenin mechanoperception". Developmental Cell. 57 (12): 1529–1544.e5. doi:10.1016/j.devcel.2022.05.001. PMID 35613615.
  33. Bazellières E, Conte V, Elosegui-Artola A, Serra-Picamal X, Bintanel-Morcillo M, Roca-Cusachs P, et al. (April 2015). "Control of cell-cell forces and collective cell dynamics by the intercellular adhesome". Nature Cell Biology. 17 (4): 409–420. doi:10.1038/ncb3135. hdl:2117/76589. PMC 4886824. PMID 25812522.
  34. Dumortier JG, Martin S, Meyer D, Rosa FM, David NB (October 2012). "Collective mesendoderm migration relies on an intrinsic directionality signal transmitted through cell contacts". Proceedings of the National Academy of Sciences of the United States of America. 109 (42): 16945–16950. Bibcode:2012PNAS..10916945D. doi:10.1073/pnas.1205870109. PMC 3479507. PMID 23027928.
  35. Grashoff C, Hoffman BD, Brenner MD, Zhou R, Parsons M, Yang MT, et al. (July 2010). "Measuring mechanical tension across vinculin reveals regulation of focal adhesion dynamics". Nature. 466 (7303): 263–266. Bibcode:2010Natur.466..263G. doi:10.1038/nature09198. PMC 2901888. PMID 20613844.
  36. Hoffman BD, Yap AS (December 2015). "Towards a Dynamic Understanding of Cadherin-Based Mechanobiology". Trends in Cell Biology. Special Issue: Quantitative Cell Biology. 25 (12): 803–814. doi:10.1016/j.tcb.2015.09.008. PMID 26519989.
  37. Ladoux B, Nelson WJ, Yan J, Mège RM (October 2015). "The mechanotransduction machinery at work at adherens junctions". Integrative Biology. 7 (10): 1109–1119. doi:10.1039/c5ib00070j. PMC 4593723. PMID 25968913.
  38. Boutillon A, Escot S, Elouin A, Jahn D, González-Tirado S, Starruß J, et al. (June 2022). "Guidance by followers ensures long-range coordination of cell migration through α-catenin mechanoperception". Developmental Cell. 57 (12): 1529–1544.e5. doi:10.1016/j.devcel.2022.05.001. PMID 35613615.
  39. Ishiyama N, Sarpal R, Wood MN, Barrick SK, Nishikawa T, Hayashi H, et al. (November 2018). "Force-dependent allostery of the α-catenin actin-binding domain controls adherens junction dynamics and functions". Nature Communications. 9 (1): 5121. Bibcode:2018NatCo...9.5121I. doi:10.1038/s41467-018-07481-7. PMC 6269467. PMID 30504777.
  40. Leerberg JM, Gomez GA, Verma S, Moussa EJ, Wu SK, Priya R, et al. (August 2014). "Tension-sensitive actin assembly supports contractility at the epithelial zonula adherens". Current Biology. 24 (15): 1689–1699. doi:10.1016/j.cub.2014.06.028. PMC 5103636. PMID 25065757.
  41. Hart KC, Tan J, Siemers KA, Sim JY, Pruitt BL, Nelson WJ, Gloerich M (July 2017). "E-cadherin and LGN align epithelial cell divisions with tissue tension independently of cell shape". Proceedings of the National Academy of Sciences of the United States of America. 114 (29): E5845–E5853. Bibcode:2017PNAS..114E5845H. doi:10.1073/pnas.1701703114. PMC 5530667. PMID 28674014.
  42. Benham-Pyle BW, Pruitt BL, Nelson WJ (May 2015). "Cell adhesion. Mechanical strain induces E-cadherin-dependent Yap1 and β-catenin activation to drive cell cycle entry". Science. 348 (6238): 1024–1027. Bibcode:2015Sci...348.1024B. doi:10.1126/science.aaa4559. PMC 4572847. PMID 26023140.
  43. Ozawa M, Hiver S, Yamamoto T, Shibata T, Upadhyayula S, Mimori-Kiyosue Y, Takeichi M (October 2020). "Adherens junction regulates cryptic lamellipodia formation for epithelial cell migration". The Journal of Cell Biology. 219 (10). doi:10.1083/jcb.202006196. PMC 7659716. PMID 32886101.
  44. Das T, Safferling K, Rausch S, Grabe N, Boehm H, Spatz JP (March 2015). "A molecular mechanotransduction pathway regulates collective migration of epithelial cells". Nature Cell Biology. 17 (3): 276–287. doi:10.1038/ncb3115. PMID 25706233. S2CID 772049.
  45. Furukawa KT, Yamashita K, Sakurai N, Ohno S (August 2017). "The Epithelial Circumferential Actin Belt Regulates YAP/TAZ through Nucleocytoplasmic Shuttling of Merlin". Cell Reports. 20 (6): 1435–1447. doi:10.1016/j.celrep.2017.07.032. PMID 28793266.
  46. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, et al. (March 2002). "Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex". Nature Cell Biology. 4 (3): 222–231. doi:10.1038/ncb758. PMID 11836526. S2CID 40423770.
  47. Vodermaier HC, Gieffers C, Maurer-Stroh S, Eisenhaber F, Peters JM (September 2003). "TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1". Current Biology. 13 (17): 1459–1468. doi:10.1016/S0960-9822(03)00581-5. PMID 12956947. S2CID 5942532.
  48. Klingelhöfer J, Troyanovsky RB, Laur OY, Troyanovsky S (August 2000). "Amino-terminal domain of classic cadherins determines the specificity of the adhesive interactions". Journal of Cell Science. 113 ( Pt 16) (16): 2829–2836. doi:10.1242/jcs.113.16.2829. PMID 10910767.
  49. Davies G, Jiang WG, Mason MD (April 2001). "HGF/SF modifies the interaction between its receptor c-Met, and the E-cadherin/catenin complex in prostate cancer cells". International Journal of Molecular Medicine. 7 (4): 385–388. doi:10.3892/ijmm.7.4.385. PMID 11254878.
  50. Daniel JM, Reynolds AB (September 1995). "The tyrosine kinase substrate p120cas binds directly to E-cadherin but not to the adenomatous polyposis coli protein or alpha-catenin". Molecular and Cellular Biology. 15 (9): 4819–4824. doi:10.1128/mcb.15.9.4819. PMC 230726. PMID 7651399.
  51. Kucerová D, Sloncová E, Tuhácková Z, Vojtechová M, Sovová V (December 2001). "Expression and interaction of different catenins in colorectal carcinoma cells". International Journal of Molecular Medicine. 8 (6): 695–698. doi:10.3892/ijmm.8.6.695. PMID 11712088.
  52. Navarro P, Lozano E, Cano A (August 1993). "Expression of E- or P-cadherin is not sufficient to modify the morphology and the tumorigenic behavior of murine spindle carcinoma cells. Possible involvement of plakoglobin". Journal of Cell Science. 105 ( Pt 4) (4): 923–934. doi:10.1242/jcs.105.4.923. hdl:10261/78716. PMID 8227214.
  53. Laoukili J, Alvarez-Fernandez M, Stahl M, Medema RH (September 2008). "FoxM1 is degraded at mitotic exit in a Cdh1-dependent manner". Cell Cycle. 7 (17): 2720–2726. doi:10.4161/cc.7.17.6580. PMID 18758239.
  54. 1 2 Yoon YM, Baek KH, Jeong SJ, Shin HJ, Ha GH, Jeon AH, et al. (September 2004). "WD repeat-containing mitotic checkpoint proteins act as transcriptional repressors during interphase". FEBS Letters. 575 (1–3): 23–29. doi:10.1016/j.febslet.2004.07.089. PMID 15388328. S2CID 21762011.
  55. Li Z, Kim SH, Higgins JM, Brenner MB, Sacks DB (December 1999). "IQGAP1 and calmodulin modulate E-cadherin function". The Journal of Biological Chemistry. 274 (53): 37885–37892. doi:10.1074/jbc.274.53.37885. PMID 10608854.
  56. Piedra J, Miravet S, Castaño J, Pálmer HG, Heisterkamp N, García de Herreros A, Duñach M (April 2003). "p120 Catenin-associated Fer and Fyn tyrosine kinases regulate beta-catenin Tyr-142 phosphorylation and beta-catenin-alpha-catenin Interaction". Molecular and Cellular Biology. 23 (7): 2287–2297. doi:10.1128/MCB.23.7.2287-2297.2003. PMC 150740. PMID 12640114.
  57. Nourry C, Maksumova L, Pang M, Liu X, Wang T (May 2004). "Direct interaction between Smad3, APC10, CDH1 and HEF1 in proteasomal degradation of HEF1". BMC Cell Biology. 5 (1): 20. doi:10.1186/1471-2121-5-20. PMC 420458. PMID 15144564.
  58. Knudsen KA, Wheelock MJ (August 1992). "Plakoglobin, or an 83-kD homologue distinct from beta-catenin, interacts with E-cadherin and N-cadherin". The Journal of Cell Biology. 118 (3): 671–679. doi:10.1083/jcb.118.3.671. PMC 2289540. PMID 1639850.
  59. Hazan RB, Kang L, Roe S, Borgen PI, Rimm DL (December 1997). "Vinculin is associated with the E-cadherin adhesion complex". The Journal of Biological Chemistry. 272 (51): 32448–32453. doi:10.1074/jbc.272.51.32448. PMID 9405455.
  60. Brady-Kalnay SM, Rimm DL, Tonks NK (August 1995). "Receptor protein tyrosine phosphatase PTPmu associates with cadherins and catenins in vivo". The Journal of Cell Biology. 130 (4): 977–986. doi:10.1083/jcb.130.4.977. PMC 2199947. PMID 7642713.
  61. Brady-Kalnay SM, Mourton T, Nixon JP, Pietz GE, Kinch M, Chen H, et al. (April 1998). "Dynamic interaction of PTPmu with multiple cadherins in vivo". The Journal of Cell Biology. 141 (1): 287–296. doi:10.1083/jcb.141.1.287. PMC 2132733. PMID 9531566.
  62. Besco JA, Hooft van Huijsduijnen R, Frostholm A, Rotter A (October 2006). "Intracellular substrates of brain-enriched receptor protein tyrosine phosphatase rho (RPTPrho/PTPRT)". Brain Research. 1116 (1): 50–57. doi:10.1016/j.brainres.2006.07.122. PMID 16973135. S2CID 23343123.
  63. Beavon IR (August 2000). "The E-cadherin-catenin complex in tumour metastasis: structure, function and regulation". European Journal of Cancer. 36 (13 Spec No): 1607–1620. doi:10.1016/S0959-8049(00)00158-1. PMID 10959047.
  64. 1 2 Weinberg R (2006). The Biology of Cancer. Garland Science. pp. 864 pages. ISBN 9780815340782. Archived from the original on 2015-09-11. Retrieved 2012-05-06.
  65. Rosen, P. Rosen's Breast Pathology, 3rd ed, 2009, p. 704. Lippincott Williams & Wilkins.
  66. Sahar DE, Behr B, Fong KD, Longaker MT, Quarto N. Unique modulation of cadherin expression pattern during posterior frontal cranial suture development and closure. Cells Tissues Organs. 2010;191(5):401-13. doi: 10.1159/000272318. Epub 2009 Dec 24. PMID 20051668; PMCID: PMC2859230.
  67. 1 2 3 Polyak K, Weinberg RA (April 2009). "Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits". Nature Reviews. Cancer. 9 (4): 265–273. doi:10.1038/nrc2620. PMID 19262571. S2CID 3336730.
  68. van der Post RS, Vogelaar IP, Carneiro F, Guilford P, Huntsman D, Hoogerbrugge N, et al. (June 2015). "Hereditary diffuse gastric cancer: updated clinical guidelines with an emphasis on germline CDH1 mutation carriers". Journal of Medical Genetics. 52 (6): 361–374. doi:10.1136/jmedgenet-2015-103094. PMC 4453626. PMID 25979631.
  69. Berx G, Cleton-Jansen AM, Nollet F, de Leeuw WJ, van de Vijver M, Cornelisse C, van Roy F (December 1995). "E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers". The EMBO Journal. 14 (24): 6107–6115. doi:10.1002/j.1460-2075.1995.tb00301.x. PMC 394735. PMID 8557030.
  70. Berx G, Cleton-Jansen AM, Strumane K, de Leeuw WJ, Nollet F, van Roy F, Cornelisse C (November 1996). "E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain". Oncogene. 13 (9): 1919–1925. PMID 8934538.
  71. Becker KF, Atkinson MJ, Reich U, Becker I, Nekarda H, Siewert JR, Höfler H (July 1994). "E-cadherin gene mutations provide clues to diffuse type gastric carcinomas". Cancer Research. 54 (14): 3845–3852. PMID 8033105.
  72. De Leeuw WJ, Berx G, Vos CB, Peterse JL, Van de Vijver MJ, Litvinov S, et al. (December 1997). "Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ". The Journal of Pathology. 183 (4): 404–411. doi:10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9. PMID 9496256. S2CID 25793212.
  73. Batlle E, Sancho E, Francí C, Domínguez D, Monfar M, Baulida J, García De Herreros A (February 2000). "The transcription factor snail is a repressor of E-cadherin gene expression in epithelial tumour cells". Nature Cell Biology. 2 (2): 84–89. doi:10.1038/35000034. PMID 10655587. S2CID 23809509.
  74. Cano A, Pérez-Moreno MA, Rodrigo I, Locascio A, Blanco MJ, del Barrio MG, et al. (February 2000). "The transcription factor snail controls epithelial-mesenchymal transitions by repressing E-cadherin expression". Nature Cell Biology. 2 (2): 76–83. doi:10.1038/35000025. hdl:10261/32314. PMID 10655586. S2CID 28329186.
  75. Comijn J, Berx G, Vermassen P, Verschueren K, van Grunsven L, Bruyneel E, et al. (June 2001). "The two-handed E box binding zinc finger protein SIP1 downregulates E-cadherin and induces invasion". Molecular Cell. 7 (6): 1267–1278. doi:10.1016/S1097-2765(01)00260-X. PMID 11430829.
  76. Hajra KM, Chen DY, Fearon ER (March 2002). "The SLUG zinc-finger protein represses E-cadherin in breast cancer". Cancer Research. 62 (6): 1613–1618. PMID 11912130.
  77. De Craene B, Gilbert B, Stove C, Bruyneel E, van Roy F, Berx G (July 2005). "The transcription factor snail induces tumor cell invasion through modulation of the epithelial cell differentiation program". Cancer Research. 65 (14): 6237–6244. doi:10.1158/0008-5472.CAN-04-3545. PMID 16024625.
  78. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, et al. (June 2004). "Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis". Cell. 117 (7): 927–939. doi:10.1016/j.cell.2004.06.006. PMID 15210113. S2CID 16181905.
  79. Eger A, Aigner K, Sonderegger S, Dampier B, Oehler S, Schreiber M, et al. (March 2005). "DeltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells". Oncogene. 24 (14): 2375–2385. doi:10.1038/sj.onc.1208429. PMID 15674322. S2CID 25818909.
  80. Liu YN, Lee WW, Wang CY, Chao TH, Chen Y, Chen JH (December 2005). "Regulatory mechanisms controlling human E-cadherin gene expression". Oncogene. 24 (56): 8277–8290. doi:10.1038/sj.onc.1208991. PMID 16116478. S2CID 12243779.
  81. 1 2 Lombaerts M, van Wezel T, Philippo K, Dierssen JW, Zimmerman RM, Oosting J, et al. (March 2006). "E-cadherin transcriptional downregulation by promoter methylation but not mutation is related to epithelial-to-mesenchymal transition in breast cancer cell lines". British Journal of Cancer. 94 (5): 661–671. doi:10.1038/sj.bjc.6602996. PMC 2361216. PMID 16495925.
  82. Graff JR, Gabrielson E, Fujii H, Baylin SB, Herman JG (January 2000). "Methylation patterns of the E-cadherin 5' CpG island are unstable and reflect the dynamic, heterogeneous loss of E-cadherin expression during metastatic progression". The Journal of Biological Chemistry. 275 (4): 2727–2732. doi:10.1074/jbc.275.4.2727. PMID 10644736.

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