The opposing roles of laminin-binding integrins in cancer

Ramovs, Veronika; Molder, Lisa te; Sonnenberg, Arnoud

doi:10.1016/j.matbio.2016.08.007

Cited by 125 publications

(116 citation statements)

References 360 publications

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“…However, the magnitude of the change (compared to vitronectin) was likely smaller for two reasons, firstly, because adhesion to vitronectin was lower than that of other ECM proteins at baseline (data not shown) and, secondly, because a greater number of integrin heterodimers (including integrin-a 3 ) have high affinity for laminin. In support of this hypothesis, adherence to collagen and fibronectin was unaltered, consistent with the constant levels in the surface expression of integrina 3 and a 4 [29,34,35].…”

Section: Discussionsupporting

confidence: 70%

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking

Prichard

Byrne

Murphy

et al. 2017

J Cellular Molecular Medi

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The fundamental mechanisms underlying erosive oesophagitis and subsequent development of Barrett's oesophagus (BO) are poorly understood. Here, we investigated the contribution of specific components of the gastric refluxate on adhesion molecules involved in epithelial barrier maintenance. Cell line models of squamous epithelium (HET‐1A) and BO (QH) were used to examine the effects of bile acids on cell adhesion to extracellular matrix proteins (Collagen, laminin, vitronectin, fibronectin) and expression of integrin ligands (α3, α4, α5, α6 and αν). Experimental findings were validated in human explant oesophageal biopsies, a rat model of gastroesophageal reflux disease (GORD) and in patient tissue microarrays. The bile acid deoxycholic acid (DCA) specifically reduced adhesion of HET‐1A cells to vitronectin and reduced cell‐surface expression of integrin‐αν via effects on endocytic recycling processes. Increased expression of integrin‐αv was observed in ulcerated tissue in a rat model of GORD and in oesophagitis and Barrett's intestinal metaplasia patient tissue compared to normal squamous epithelium. Increased expression of integrin‐αν was observed in QH BO cells compared to HET‐1A cells. QH cells were resistant to DCA‐mediated loss of adhesion and reduction in cell‐surface expression of integrin‐αν. We demonstrated that a specific component of the gastric refluxate, DCA, affects the epithelial barrier through modulation of integrin αν expression, providing a novel mechanism for bile acid‐mediated erosion of oesophageal squamous epithelium and promotion of BO. Strategies aimed at preventing bile acid‐mediated erosion should be considered in the clinical management of patients with GORD.

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Section: Discussionsupporting

confidence: 70%

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking

Prichard

Byrne

Murphy

et al. 2017

J Cellular Molecular Medi

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“…Ligand. To test the role of ligand binding in αvβ3 integrin alignment, we plated cells expressing αV-GFP-constrained and paxillinmCherry on either poly-L-lysine (PLL) to mediate nonspecific cell adhesion (19) or laminin that is not an αvβ3 ligand (20). TIRFM images of paxillin-mCherry showed that PLL inhibited FA formation, although rapid FN secretion by MEFs precluded complete FA abolition, while MEFs on laminin had robust paxillin-containing FA with poor enrichment of αV-GFP-constrained ( Fig.…”

Section: Resultsmentioning

confidence: 99%

Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions

Swaminathan

Kalappurakkal

Mehta

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

112

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Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization-or contractilitydriven "retrograde flow" of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues.cell migration | mechanosensing | fluorescence polarization microscopy

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“…S2a). This implies a switch in dimer pairs, as integrin α 6 preferentially dimerizes with integrin β 4 over integrin β 1 [43]. This is an important finding, as α 6 β 4 is known to be important in cancer cell motility and invasion [44].…”

Section: Cells Maximize Expression Of Integrin α 6 and Extracellularmentioning

confidence: 95%

Integrin α₆and EGFR Signaling Converge at Mechanosensitive Calpain 2

Schwartz

Hall

Barney

et al. 2017

Preprint

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The opposing roles of laminin-binding integrins in cancer

Cited by 125 publications

References 360 publications

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking

Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions

Integrin α₆and EGFR Signaling Converge at Mechanosensitive Calpain 2

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The opposing roles of laminin-binding integrins in cancer

Cited by 125 publications

References 360 publications

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking

Deoxycholic acid promotes development of gastroesophageal reflux disease and Barrett's oesophagus by modulating integrin‐αv trafficking

Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions

Integrin α6and EGFR Signaling Converge at Mechanosensitive Calpain 2

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Integrin α₆and EGFR Signaling Converge at Mechanosensitive Calpain 2