Coordinate Recruitment of E-Cadherin and ALCAM to Cell–Cell Contacts by α-Catenin

Tomita, K.; Bokhoven, Adrie van; Jansen, Cornelius F.J.; Bussemakers, M. J. G.; Schalken, Jack A.

doi:10.1006/bbrc.1999.2040

Cited by 55 publications

(51 citation statements)

References 19 publications

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“…Tomita and co-workers reported that ALCAM is corecruited to sites of cell-cell contact upon correct assembly of E-cadherin/α-catenin complexes in epithelial cells (Tomita et al, 2000). Catenins link cadherins and, for example, PECAM-1 to the actin cytoskeleton (Ilan et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Zimmerman

Nelissen

Vries³

et al. 2004

Journal of Cell Science

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The activated leukocyte cell adhesion molecule (ALCAM) is dynamically regulated by the actin cytoskeleton. In this study we explored the molecular mechanisms and signaling pathways underlying the cytoskeletal restraints of this homotypic adhesion molecule. We observed that ALCAM-mediated adhesion induced by cytoskeleton-disrupting agents is accompanied by activation of the small GTPases RhoA, Rac1 and Cdc42. Interestingly, unlike adhesion mediated by integrins or cadherins, ALCAM-mediated adhesion appears to be independent of Rho-like GTPase activity. By contrast, we demonstrated that protein kinase C (PKC) plays a major role in ALCAM-mediated adhesion. PKC inhibition by chelerythrine chloride and myristoylated PKC pseudosubstrate, as well as PKC downregulation by PMA strongly reduce cytoskeleton-dependent ALCAM-mediated adhesion. Since serine and threonine residues are dispensable for ALCAM-mediated adhesion and ALCAM is not phosphorylated, we can rule out that ALCAM itself is a direct PKC substrate. We conclude that PKCα plays a dominant role in cytoskeleton-dependent avidity modulation of ALCAM.

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Section: Discussionmentioning

confidence: 99%

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Zimmerman

Nelissen

Vries³

et al. 2004

Journal of Cell Science

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“…Expression of α-catenin was demonstrated to be associated with melanoma invasiveness and metastasis (Zhang and Hersey, 1999). Moreover, α-catenin, which is an essential element of the E-cadherin invasion suppressor complex, has indeed been shown to affect ALCAM localization to cell-cell contact sites in prostate cancer cells (Tomita et al, 2000). In this regard, we examined both expression and cellular localization of α-catenin in the respective melanoma cells.…”

Section: α-Catenin May Be the Link Between F-actin And Alcammentioning

confidence: 99%

The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism

Uhlenbrock

Eberth

Herbrand

et al. 2004

Journal of Cell Science

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Rho-like GTPases such as RhoA, Rac1 and Cdc42 are key regulators of actin-dependent cell functions including cell morphology, adhesion and migration. Tiam1 (T lymphoma invasion and metastasis 1), a guanine nucleotide exchange factor that activates Rac, is an important regulator of cell shape and invasiveness in epithelial cells and fibroblasts. Overexpression of Tiam1 in metastatic melanoma cells converted the constitutive mesenchymal phenotype into an epithelial-like phenotype. This included the induction of stringent cell-cell contacts mediated by the Ig-like receptor ALCAM (activated leukocyte cell adhesion molecule) and actin redistribution to cell-cell junctions. This phenotypic switch was dependent on increased Rac but not Rho activity, and on the redistribution and adhesive function of ALCAM, whereas cadherins were not involved. Although cell proliferation was significantly enhanced, the gain of cell-cell junctions strongly counteracted cell motility and invasion as shown for two- and three-dimensional collagen assays as well as invasion into human skin reconstructs. The reverse transition from mesenchymal invasive to a resident epithelial-like phenotype implicates a role for Tiam1/Rac signaling in the control of cell-cell contacts through a novel ALCAM-mediated mechanism.

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“…Also CD166 is involved in regulation the formation of cell-cell contacts [48,49]. Even though the function of the debated CSC marker CD133 remains unknown, its presence in plasma membrane protrusions [50,51] as well as its ability to interact with plasma membrane cholesterol [52] suggests that the protein might play a role in establishing and maintaining plasmamembrane protrusions.…”

Section: Function Of Csc Markers and Their Relevance To Csc Biologymentioning

confidence: 99%

Molecular identification and targeting of colorectal cancer stem cells

2010

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AbstrAct:Tumor initiating or cancer stem cells (CSCs) are suggested to be responsible for tumor initiation and growth. Moreover, therapy resistance and minimal residual disease are thought to result from selective resistance of CSCs. Isolation of CSCs from colon carcinomas can be accomplished by selection of a subpopulation of tumor cells based on expression of one or multiple cell surface markers associated with cancer stemness, like CD133, CD44, CD24, CD29, CD166 and Lgr5. Identification of colon CSCs will lead to a better rational for new therapies that aim to target this fraction specifically. In this review, we analyze known markers used for selection of colon CSCs and their potential function in CSC biology. Moreover, we discuss potential targeting strategies for eradicating CSCs specifically in order to develop more effective therapeutic strategies as well as to address more fundamental questions like the actual role of CSCs in tumor growth.

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Coordinate Recruitment of E-Cadherin and ALCAM to Cell–Cell Contacts by α-Catenin

Cited by 55 publications

References 19 publications

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

Cytoskeletal restraints regulate homotypic ALCAM-mediated adhesion through PKCα independently of Rho-like GTPases

The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism

Molecular identification and targeting of colorectal cancer stem cells

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