Folliculin, the Product of the Birt-Hogg-Dube Tumor Suppressor Gene, Interacts with the Adherens Junction Protein p0071 to Regulate Cell-Cell Adhesion

Cells must cooperate and communicate to form a multicellular animal. Information about the molecules required for these processes have come from a variety of sources; the convergence between the studies of particular molecules by vertebrate cell biologists and the genes identified by scientists investigating development in Drosophila has been especially fruitful. We are interested in the connection between cadherin proteins that regulate cell-cell adhesion and the wingless/wnt-1 cell-cell signaling molecules controlling pattern formation during development. The Drosophila segment polarity gene armadillo, homolog of the vertebrate adherens junction protein-catenin, is required for both cell adhesion and wg signaling. We review what is known about wingless signaling in Drosophila, and discuss the role of cell-cell junctions in both cell adhesion and cell communication. We then describe the results of our preliminary structure-function analysis of Armadillo protein in both cell adhesion and wingless signaling. Finally, we discuss evidence supporting a direct role for Armadillo and adherens junction in transduction of wingless signal.

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Hoxc8 downregulates Mgl1 tumor suppressor gene expression and reduces its concomitant function on cell adhesion

Molecules and Cells ◽

10.1007/s10059-011-0069-8 ◽

2011 ◽

Vol 32 (3) ◽

pp. 273-279 ◽

Cited By ~ 7

Author(s):

Kalyani Ruthala ◽

Jogeswar Gadi ◽

Ji-Yeon Lee ◽

Heejei Yoon ◽

Hyun Joo Chung ◽

...

Keyword(s):

Gene Expression ◽

Cell Adhesion ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Suppressor Gene

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E-cadherin and APC compete for the interaction with beta-catenin and the cytoskeleton.

The Journal of Cell Biology ◽

10.1083/jcb.127.6.2061 ◽

1994 ◽

Vol 127 (6) ◽

pp. 2061-2069 ◽

Cited By ~ 386

Author(s):

J Hülsken ◽

W Birchmeier ◽

J Behrens

Keyword(s):

Cell Adhesion ◽

Tumor Suppressor ◽

Tumor Suppressor Gene ◽

Gene Product ◽

Suppressor Gene ◽

Cell Junctions ◽

Beta Catenin ◽

Tumor Suppressor Gene Product ◽

Product Forms ◽

E Cadherin

beta-Catenin is involved in the formation of adherens junctions of mammalian epithelia. It interacts with the cell adhesion molecule E-cadherin and also with the tumor suppressor gene product APC, and the Drosophila homologue of beta-catenin, armadillo, mediates morphogenetic signals. We demonstrate here that E-cadherin and APC directly compete for binding to the internal, armadillo-like repeats of beta-catenin; the NH2-terminal domain of beta-catenin mediates the interaction of the alternative E-cadherin and APC complexes to the cytoskeleton by binding to alpha-catenin. Plakoglobin (gamma-catenin), which is structurally related to beta-catenin, mediates identical interactions. We thus show that the APC tumor suppressor gene product forms strikingly similar associations as found in cell junctions and suggest that beta-catenin and plakoglobin are central regulators of cell adhesion, cytoskeletal interaction, and tumor suppression.

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Tuberin, the tuberous sclerosis complex 2 tumor suppressor gene product, regulates Rho activation, cell adhesion and migration

Oncogene ◽

10.1038/sj.onc.1205962 ◽

2002 ◽

Vol 21 (55) ◽

pp. 8470-8476 ◽

Cited By ~ 90

Author(s):

Aristotelis Astrinidis ◽

Timothy P Cash ◽

Deborah S Hunter ◽

Cheryl L Walker ◽

Jonathan Chernoff ◽

...

Keyword(s):

Cell Adhesion ◽

Tumor Suppressor ◽

Tuberous Sclerosis ◽

Tumor Suppressor Gene ◽

Gene Product ◽

Tuberous Sclerosis Complex ◽

Suppressor Gene ◽

Tumor Suppressor Gene Product ◽

Cell Adhesion And Migration ◽

And Migration

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Downregulation of Rap1GAP in Human Tumor Cells Alters Cell/Matrix and Cell/Cell Adhesion

Molecular and Cellular Biology ◽

10.1128/mcb.01345-09 ◽

2010 ◽

Vol 30 (13) ◽

pp. 3262-3274 ◽

Cited By ~ 29

Author(s):

Oxana M. Tsygankova ◽

Changqing Ma ◽

Waixing Tang ◽

Christopher Korch ◽

Michael D. Feldman ◽

...

Keyword(s):

Cell Adhesion ◽

Tumor Cells ◽

Adherens Junction ◽

Protein Distribution ◽

P120 Catenin ◽

Cell Contacts ◽

Cell Matrix ◽

Junction Protein ◽

E Cadherin ◽

Cell Cell

ABSTRACT Rap1GAP expression is decreased in human tumors. The significance of its downregulation is unknown. We show that Rap1GAP expression is decreased in primary colorectal carcinomas. To elucidate the advantages conferred on tumor cells by loss of Rap1GAP, Rap1GAP expression was silenced in human colon carcinoma cells. Suppressing Rap1GAP induced profound alterations in cell adhesion. Rap1GAP-depleted cells exhibited defects in cell/cell adhesion that included an aberrant distribution of adherens junction proteins. Depletion of Rap1GAP enhanced adhesion and spreading on collagen. Silencing of Rap expression normalized spreading and restored E-cadherin, β-catenin, and p120-catenin to cell/cell contacts, indicating that unrestrained Rap activity underlies the alterations in cell adhesion. The defects in adherens junction protein distribution required integrin signaling as E-cadherin and p120-catenin were restored at cell/cell contacts when cells were plated on poly-l-lysine. Unexpectedly, Src activity was increased in Rap1GAP-depleted cells. Inhibition of Src impaired spreading and restored E-cadherin at cell/cell contacts. These findings provide the first evidence that Rap1GAP contributes to cell/cell adhesion and highlight a role for Rap1GAP in regulating cell/matrix and cell/cell adhesion. The frequent downregulation of Rap1GAP in epithelial tumors where alterations in cell/cell and cell/matrix adhesion are early steps in tumor dissemination supports a role for Rap1GAP depletion in tumor progression.

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Armadillo is required for adherens junction assembly, cell polarity, and morphogenesis during Drosophila embryogenesis.

The Journal of Cell Biology ◽

10.1083/jcb.134.1.133 ◽

1996 ◽

Vol 134 (1) ◽

pp. 133-148 ◽

Cited By ~ 203

Author(s):

R T Cox ◽

C Kirkpatrick ◽

M Peifer

Keyword(s):

Cell Adhesion ◽

Epithelial Cells ◽

Embryonic Development ◽

Cell Polarity ◽

Adherens Junctions ◽

Adherens Junction ◽

Morphogenetic Movements ◽

Junction Protein ◽

Normal Embryonic Development ◽

Cell Cell

Morphological and biochemical analyses have identified a set of proteins which together form a structure known as the adherens junction. Elegant experiments in tissue culture support the idea that adherens junctions play a key role in cell-cell adhesion and in organizing cells into epithelia. During normal embryonic development, cells quickly organize epithelia; these epithelial cells participate in many of the key morphogenetic movements of gastrulation. This prompted the hypothesis that adherens junctions ought to be critical for normal embryonic development. Drosophila Armadillo, the homologue of vertebrate beta-catenin, is a core component of the adherens junction protein complex and has been hypothesized to be essential for adherens junction function in vivo. We have used an intermediate mutant allele of armadillo, armadilloXP33, to test these hypotheses in Drosophila embryos. Adherens junctions cannot assemble in the absence of Armadillo, leading to dramatic defects in cell-cell adhesion. The epithelial cells of the embryo lose adhesion to each other, round up, and apparently become mesenchymal. Mutant cells also lose their normal cell polarity. These disruptions in the integrity of epithelia block the appropriate morphogenetic movements of gastrulation. These results provide the first demonstration of the effect of loss of adherens junctions on Drosophila embryonic development.

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