EGFR and β1 integrins utilize different signaling pathways to activate Akt

Velling, Teet; Stefansson, Anne; Johansson, Staffan

doi:10.1016/j.yexcr.2007.08.018

Cited by 25 publications

(18 citation statements)

References 44 publications

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“…Other mechanisms need to be identified. Since integrins have been shown to induce Akt [42, 43] and ERK phosphorylation [44], it is also possible that TMEFF2 modulates MAPK and PI3K pathways via its effects on integrin expression establishing a negative feedback loop. This would suggest that TMEFF2 may modulate the cross-talk between integrins and growth factor receptors to control cellular responses including survival, growth, differentiation and migration.…”

Section: Discussionmentioning

confidence: 99%

The TMEFF2 tumor suppressor modulates integrin expression, RhoA activation and migration of prostate cancer cells

Chen

Corbin

Tipton

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Cell adhesion and migration play important roles in physiological and pathological states, including embryonic development and cancer invasion and metastasis. The type I transmembrane protein with epidermal growth factor and two follistatin motifs 2 (TMEFF2) is expressed mainly in brain and prostate and its expression is deregulated in prostate cancer. We have previously shown that TMEFF2 can function as a tumor suppressor by inhibiting cell migration and invasion of prostate cells. However, the molecular mechanisms involved in this inhibition are not clear. In this study we demonstrate that TMEFF2 affects cell adhesion and migration of prostate cancer cells and that this effect correlates with changes in integrin expression and RhoA activation. Deletion of a 13 basic-rich amino acid region in the cytoplasmic domain of TMEFF2 prevented these effects. Overexpression of TMEFF2 reduced cell attachment and migration on vitronectin and caused a concomitant decrease in RhoA activation, stress fiber formation and expression of αv, β1 and β3 integrin subunits. Conversely, TMEFF2 interference in 22Rv1 prostate cancer cells resulted in increased integrin expression. Results obtained with a double TRAMP/TMEFF2 transgenic mouse also indicated that TMEFF2 expression reduced integrin expression in the mouse prostate. In summary, the data presented here indicate an important role of TMEFF2 in regulating cell adhesion and migration that involves integrin signaling and is mediated by its cytoplasmic domain.

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Section: Discussionmentioning

confidence: 99%

The TMEFF2 tumor suppressor modulates integrin expression, RhoA activation and migration of prostate cancer cells

Chen

Corbin

Tipton

et al. 2014

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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“…Analogously, maintenance of epithelial polarity in tissues may require the continued sensing of polarizing cues, such as detecting the ECM through integrins and detecting cell neighbours through cadherins. Notably, both of these receptors can control the generation of PtdIns(3,4,5)P 3 12,42–44, which has a fundamental role in generating and maintaining basolateral membrane identity (BOX 2), at least in MDCK cells. Cadherin and integrin receptors can signal through small GTPases, such as to the Rho and Arf families, which can function both upstream and downstream of PtdInsP.…”

Section: Orientating Polarity: Ecm and Gtpase Signallingmentioning

confidence: 99%

From cells to organs: building polarized tissue

Bryant

Mostov

2008

Nat Rev Mol Cell Biol

702

730

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How do animal cells assemble into tissues and organs? A diverse array of tissue structures and shapes can be formed by organizing groups of cells into different polarized arrangements and by coordinating their polarity in space and time. Conserved design principles underlying this diversity are emerging from studies of model organisms and tissues. We discuss how conserved polarity complexes, signalling networks, transcription factors, membrane-trafficking pathways, mechanisms for forming lumens in tubes and other hollow structures, and transitions between different types of polarity, such as between epithelial and mesenchymal cells, are used in similar and iterative manners to build all tissues.The defining feature of metazoa is that their cells are organized into multicellular tissues and organs. Although almost every eukaryotic cell is spatially asymmetric or polarized, polarity must be coordinated in space and time for individual cells to form a tissue 1 . Cell polarity involves the asymmetric organization of most of the physical aspects of the cell, including the cell surface, intracellular organelles and the cytoskeleton 2,3 . Analysis of the polarization of unicellular eukaryotes, such as yeast, has yielded enormous insights into the mechanisms that underlie the polarity of individual cells 3 . Formation of a tissue, however, requires an ensemble cast; the emergent properties of the tissue result from the combined roles of the individual cells that are involved. Accordingly, several biological processes, including cell division, cell death, shape changes, cell migration and differentiation, must be coordinated with the polarity requirements of a tissue to form an organ 4 .Evolutionarily, epithelia are the most archetypal polarized tissues in metazoa, with ~60% of mammalian cell types being of epithelial or epithelial-derived origin 5 . Accordingly, the best studied polarized tissue is the simple epithelium of the mammalian intestine and kidney, the cells of which are columnar in shape (that is, they are taller than they are wide). The apical surfaces of these cells provide the luminal interface and are specialized to regulate the exchange of materials, such as nutrients from the intestine. The lateral surfaces of these cells contact adjacent cells and have specialized junctions and cell-cell adhesion structures 3,6 (FIG. 1a). The basal surfaces of these cells contact the underlying basement membrane, extracellular matrix (ECM) and, ultimately, underlying blood vessels. The basal and lateral surfaces are fairly similar in composition and organization and are often referred to together as the basolateral surface. The apical and basolateral surfaces, however, have very different NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript compositions. In vertebrates, tight junctions (TJs) are found at the apical-most portion of the lateral surfaces, where the TJs form barriers both between the apical and basolateral surfaces and between adjacent cells, limiting paracellular permeability...

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“…1-3) and integrin-induced activation of the PI3K-AKT pathway (24,33,35) and the ability of heparanase to activate integrins (16,36), we examined whether increased AKT phosphorylation by heparanase involved integrins. Addition of heparanase to adherent MCF7 cells resulted in ϳ5-fold increased AKT phosphorylation (Fig.…”

Section: Heparanase-induced Akt Activation Is Blocked By Pp2 But Invomentioning

confidence: 99%

Characterization of Heparanase-induced Phosphatidylinositol 3-Kinase-AKT Activation and Its Integrin Dependence

Riaz

Ilan²,

Vlodavsky³

et al. 2013

Journal of Biological Chemistry

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Background: Heparanase levels are associated with tumor metastasis. Latent heparanase induces the prosurvival PI3K-AKT pathway via uncharacterized mechanisms. Results: AKT activation by heparanase involved PI3K p110␣, RAS, RICTOR, a PP2-sensitive kinase, FAK or PYK2, and ␤1 or ␤3 integrin-mediated adhesion. Conclusion:The heparanase receptor(s) intimately cooperates with integrins during induction of the PI3K-AKT pathway. Significance: Key steps in the heparanase-PI3K-AKT axis were identified.

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EGFR and β1 integrins utilize different signaling pathways to activate Akt

Cited by 25 publications

References 44 publications

The TMEFF2 tumor suppressor modulates integrin expression, RhoA activation and migration of prostate cancer cells

The TMEFF2 tumor suppressor modulates integrin expression, RhoA activation and migration of prostate cancer cells

From cells to organs: building polarized tissue

Characterization of Heparanase-induced Phosphatidylinositol 3-Kinase-AKT Activation and Its Integrin Dependence

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