Fetal Brain Subdivisions Defined by R- and E-Cadherin Expressions: Evidence for the Role of Cadherin Activity in Region-Specific, Cell–Cell Adhesion

Increasing levels of angiogenesis play an important role in the pathogenesis and progression of multiple myeloma (MM). Malignant plasma cells promote a gradual increase in the degree of angiogenesis, modulation of specific cell-cell adhesion molecules and secretion of matrix-metallo-proteinases (MMPs), changing the BM composition from benign conditions, such as MGUS, to smouldering multiple myeloma (SM) and to active MM. We aimed to identify a gene expression profile, helpful to discriminate the “angiogenic potential” in BM and PB plasma cells from MGUS, SMM and active MM patients analyzed at diagnosis. We analyzed the expression of cell-cell adhesion molecules such as VE-Cadherin, E-Cadherin MCAM/MUC18/CD146 and of the MMP-2 and MMP-9. MCAM/MUC18 expression resulted mostly associated with that of the pivotal angiogenic factors VEGF and Ang2, and in MGUS the pattern was different in steady state, compared to progression towards SM. Furthermore, E-Cadherin, the main epithelial cell-cell-adhesion molecule, unexpectedly resulted overexpressed in MM.

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CD151 regulates epithelial cell–cell adhesion through PKC- and Cdc42-dependent actin cytoskeletal reorganization

The Journal of Cell Biology ◽

10.1083/jcb.200301075 ◽

2003 ◽

Vol 163 (1) ◽

pp. 165-176 ◽

Cited By ~ 90

Author(s):

Masaki Shigeta ◽

Noriko Sanzen ◽

Masayuki Ozawa ◽

Jianguo Gu ◽

Hitoshi Hasegawa ◽

...

Keyword(s):

Cell Adhesion ◽

Epithelial Cell ◽

Cytoskeletal Reorganization ◽

Cortical Actin ◽

A431 Cells ◽

Kinase C ◽

Integrin Α3β1 ◽

E Cadherin ◽

Cell Cell

CD151, a member of the tetraspanin family proteins, tightly associates with integrin α3β1 and localizes at basolateral surfaces of epithelial cells. We found that overexpression of CD151 in A431 cells accelerated intercellular adhesion, whereas treatment of cells with anti-CD151 mAb perturbed the integrity of cortical actin filaments and cell polarity. E-Cadherin puncta formation, indicative of filopodia-based adhesion zipper formation, as well as E-cadherin anchorage to detergent-insoluble cytoskeletal matrix, was enhanced in CD151-overexpressing cells. Levels of GTP-bound Cdc42 and Rac were also elevated in CD151-overexpressing cells, suggesting the role of CD151 in E-cadherin–mediated cell–cell adhesion as a modulator of actin cytoskeletal reorganization. Consistent with this possibility, engagement of CD151 by the substrate-adsorbed anti-CD151 mAb induced prominent Cdc42-dependent filopodial extension, which along with E-cadherin puncta formation, was strongly inhibited by calphostin C, a protein kinase C (PKC) inhibitor. Together, these results indicate that CD151 is involved in epithelial cell–cell adhesion as a modulator of PKC- and Cdc42-dependent actin cytoskeletal reorganization.

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Mouse proximal tubular cell-cell adhesion inhibits apoptosis by a cadherin-dependent mechanism

AJP Renal Physiology ◽

10.1152/ajprenal.2000.278.5.f758 ◽

2000 ◽

Vol 278 (5) ◽

pp. F758-F768 ◽

Cited By ~ 54

Author(s):

Eoin Bergin ◽

Jerrold S. Levine ◽

Jason S. Koh ◽

Wilfred Lieberthal

Keyword(s):

Cell Adhesion ◽

Primary Cultures ◽

Cell Aggregation ◽

Cell Matrix ◽

Proximal Tubular ◽

Cell Matrix Interactions ◽

Suspended Cells ◽

E Cadherin ◽

Cell Cell

Adhesion of epithelial cells to matrix is known to inhibit apoptosis. However, the role of cell-cell adhesion in mediating cell survival remains uncertain. Primary cultures of mouse proximal tubular (MPT) cells were used to examine the role of cell-cell adhesion in promoting survival. When MPT cells were deprived of both cell-matrix and cell-cell adhesion, they died by apoptosis. However, when incubated in agarose-coated culture dishes (to prevent cell-matrix adhesion) and at high cell density (to allow cell-cell interactions), MPT cells adhered to one another and remained viable. Expression of E-cadherin among suspended, aggregating cells increased with time. A His-Ala-Val (HAV)-containing peptide that inhibits homophilic E-cadherin binding prevented cell-cell aggregation and promoted apoptosis of MPT cells in suspension. By contrast, inhibition of potential β1-integrin-mediated interactions between cells in suspension did not prevent either aggregation or survival of suspended cells. Aggregation of cells in suspension activated phosphatidylinositol 3-kinase (PI3K), an event that was markedly reduced by the presence of the HAV peptide. LY-294002, an inhibitor of PI3K, also inhibited survival of suspended cells. In summary, we provide novel evidence that MPT cells, when deprived of normal cell-matrix interactions, can adhere to one another in a cadherin-dependent fashion and remain viable. Survival of aggregated cells depends on activation of PI3K.

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Role of Cadherins in Cancer—A Review

International Journal of Molecular Sciences ◽

10.3390/ijms21207624 ◽

2020 ◽

Vol 21 (20) ◽

pp. 7624

Author(s):

Ilona Kaszak ◽

Olga Witkowska-Piłaszewicz ◽

Zuzanna Niewiadomska ◽

Bożena Dworecka-Kaszak ◽

Felix Ngosa Toka ◽

...

Keyword(s):

Cell Adhesion ◽

Tumor Progression ◽

Signaling Pathways ◽

Rho Gtpases ◽

Epithelial Mesenchymal Transition ◽

Clinical Importance ◽

Mesenchymal Transition ◽

E Cadherin ◽

Cell Cell

Cadherins play an important role in tissue homeostasis, as they are responsible for cell-cell adhesion during embryogenesis, tissue morphogenesis, differentiation and carcinogenesis. Cadherins are inseparably connected with catenins, forming cadherin-catenin complexes, which are crucial for cell-to-cell adherence. Any dysfunction or destabilization of cadherin-catenin complex may result in tumor progression. Epithelial mesenchymal transition (EMT) is a mechanism in which epithelial cadherin (E-cadherin) expression is lost during tumor progression. However, during tumorigenesis, many processes take place, and downregulation of E-cadherin, nuclear β-catenin and p120 catenin (p120) signaling are among the most critical. Additional signaling pathways, such as Receptor tyrosine kinase (RTK), Rho GTPases, phosphoinositide 3-kinase (PI3K) and Hippo affect cadherin cell-cell adhesion and also contribute to tumor progression and metastasis. Many signaling pathways may be activated during tumorigenesis; thus, cadherin-targeting drugs seem to limit the progression of malignant tumor. This review discusses the role of cadherins in selected signaling mechanisms involved in tumor growth. The clinical importance of cadherin will be discussed in cases of human and animal cancers.

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Role of IQGAP1, a Target of the Small GTPases Cdc42 and Rac1, in Regulation of E-Cadherin- Mediated Cell-Cell Adhesion

10.1126/science.281.5378.832 ◽

1998 ◽

Vol 281 (5378) ◽

pp. 832-835 ◽

Cited By ~ 359

Author(s):

S. Kuroda

Keyword(s):

Cell Adhesion ◽

Small Gtpases ◽

E Cadherin ◽

Cell Cell

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A Novel Role of Nectins in Inhibition of the E-Cadherin–induced Activation of Rac and Formation of Cell-Cell Adherens Junctions

Molecular Biology of the Cell ◽

10.1091/mbc.e03-05-0321 ◽

2004 ◽

Vol 15 (3) ◽

pp. 1077-1088 ◽

Cited By ~ 35

Author(s):

Takashi Hoshino ◽

Kazuya Shimizu ◽

Tomoyuki Honda ◽

Tomomi Kawakatsu ◽

Taihei Fukuyama ◽

...

Keyword(s):

Cell Adhesion ◽

G Protein ◽

Adherens Junctions ◽

Resonance Energy Transfer ◽

Resonance Energy ◽

Inhibitory Effect ◽

Small G Protein ◽

E Cadherin ◽

Cell Cell

Nectins are Ca2+-independent immunoglobulin (Ig)-like cell-cell adhesion molecules. The trans-interactions of nectins recruit cadherins to the nectin-based cell-cell adhesion, resulting in formation of cell-cell adherens junctions (AJs) in epithelial cells and fibroblasts. The trans-interaction of E-cadherin induces activation of Rac small G protein, whereas the trans-interactions of nectins induce activation of not only Rac but also Cdc42 small G protein. We showed by the fluorescent resonance energy transfer (FRET) imaging that the trans-interaction of E-cadherin induced dynamic activation and inactivation of Rac, which led to dynamic formation and retraction of lamellipodia. Moreover, we found here that the nectins, which did not trans-interact with other nectins (non–trans-interacting nectins), inhibited the E-cadherin–induced activation of Rac and reduced the velocity of the formation of the E-cadherin-based cell-cell AJs. The inhibitory effect of non–trans-interacting nectins was suppressed by the activation of Cdc42 induced by the trans-interactions of nectins. These results indicate a novel role of nectins in regulation of the E-cadherin–induced activation of Rac and formation of cell-cell AJs.

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E-cadherin represses anchorage-independent growth in sarcomas through both signaling and mechanical mechanisms

10.1101/347815 ◽

2018 ◽

Author(s):

Mohit Kumar Jolly ◽

Kathryn E Ware ◽

Shengnan Xu ◽

Shivee Gilja ◽

Samantha Shetler ◽

...

Keyword(s):

Cell Adhesion ◽

Intracellular Signaling ◽

Epithelial Mesenchymal Transition ◽

Migration And Invasion ◽

Specific Cell ◽

Mesenchymal Transition ◽

Anchorage Independent Growth ◽

Sarcoma Cells ◽

E Cadherin ◽

Cell Cell

E-cadherin, an epithelial-specific cell-cell adhesion molecule, plays multiple roles in maintaining adherens junctions, regulating migration and invasion, and mediating intracellular signaling. Downregulation of E-cadherin is a hallmark of epithelial-mesenchymal transition (EMT) and correlates with poor prognosis in multiple carcinomas. Conversely, upregulation of E-cadherin is prognostic for improved survival in sarcomas. Yet, despite the prognostic benefit of E-cadherin expression in sarcoma, the mechanistic significance of E-cadherin in sarcomas remains poorly understood. Here, by combining mathematical models with wet-bench experiments, we identify the core regulatory networks mediated by E-cadherin in sarcomas, and decipher their functional consequences. Unlike in carcinomas, E-cadherin overexpression in sarcomas does not induce a mesenchymal-epithelial transition (MET). However, E-cadherin acts to reduce both anchorage-independent growth and spheroid formation of sarcoma cells. Ectopic E-cadherin expression acts to downregulate phosphorylated CREB (p-CREB) and the transcription factor, TBX2, to inhibit anchorage-independent growth. RNAi-mediated knockdown of TBX2 phenocopies the effect of E-cadherin on p-CREB levels and restores sensitivity to anchorage-independent growth in sarcoma cells. Beyond its signaling role, E-cadherin expression in sarcoma cells can also strengthen cell-cell adhesion and restricts spheroid growth through mechanical action. Together, our results demonstrate that E-cadherin inhibits sarcoma aggressiveness by preventing anchorage-independent growth.

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E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells.

The Journal of Cell Biology ◽

10.1083/jcb.113.1.173 ◽

1991 ◽

Vol 113 (1) ◽

pp. 173-185 ◽

Cited By ~ 1012

Author(s):

U H Frixen ◽

J Behrens ◽

M Sachs ◽

G Eberle ◽

B Voss ◽

...

Keyword(s):

Cell Adhesion ◽

Cell Lines ◽

Carcinoma Cell ◽

Northern Blotting ◽

Carcinoma Cells ◽

Specific Cell ◽

Human Carcinoma ◽

Carcinoma Cell Lines ◽

E Cadherin ◽

Cell Cell

The ability of carcinomas to invade and to metastasize largely depends on the degree of epithelial differentiation within the tumors, i.e., poorly differentiated being more invasive than well-differentiated carcinomas. Here we confirmed this correlation by examining various human cell lines derived from bladder, breast, lung, and pancreas carcinomas. We found that carcinoma cell lines with an epithelioid phenotype were noninvasive and expressed the epithelium-specific cell-cell adhesion molecule E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80), as visualized by immunofluorescence microscopy and by Western and Northern blotting, whereas carcinoma cell lines with a fibroblastoid phenotype were invasive and had lost E-cadherin expression. Invasiveness of these latter cells could be prevented by transfection with E-cadherin cDNA and was again induced by treatment of the transfected cells with anti-E-cadherin mAbs. These findings indicate that the selective loss of E-cadherin expression can generate dedifferentiation and invasiveness of human carcinoma cells, and they suggest further that E-cadherin acts as an invasion suppressor.

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