Temporal changes in the expression and distribution of adhesion molecules during liver development and regeneration.

Stamatoglou, S.C.; Enrich, Carlos; Manson, Margaret M.; Hughes, R. Colin

doi:10.1083/jcb.116.6.1507

Cited by 58 publications

(50 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also, in hepatocytes, which contain large amounts of AnxA6 in endosomes (58), the level of ECM proteins (FN and laminin) correlates with the cell surface expression of their cognate integrins or adhesion molecules (59,60). Actually, we provided the first evidence for the hepatic endocytic compartment modulating the ECM (1).…”

Section: Discussionmentioning

confidence: 80%

Annexin A6 and Late Endosomal Cholesterol Modulate Integrin Recycling and Cell Migration

García-Melero

Reverter

Hoque

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

Annexins are a family of proteins that bind to phospholipids in a calcium-dependent manner. Earlier studies implicated annexin A6 (AnxA6) to inhibit secretion and participate in the organization of the extracellular matrix. We recently showed that elevated AnxA6 levels significantly reduced secretion of the extracellular matrix protein fibronectin (FN). Because FN is directly linked to the ability of cells to migrate, this prompted us to investigate the role of AnxA6 in cell migration. Up-regulation of AnxA6 in several cell models was associated with reduced cell migration in wound healing, individual cell tracking and threedimensional migration/invasion assays. The reduced ability of AnxA6-expressing cells to migrate was associated with decreased cell surface expression of ␣V␤3 and ␣5␤1 integrins, both FN receptors. Mechanistically, we found that elevated AnxA6 levels interfered with syntaxin-6 (Stx6)-dependent recycling of integrins to the cell surface. AnxA6 overexpression caused mislocalization and accumulation of Stx6 and integrins in recycling endosomes, whereas siRNA-mediated AnxA6 knockdown did not modify the trafficking of integrins. Given our recent findings that inhibition of cholesterol export from late endosomes (LEs) inhibits Stx6-dependent integrin recycling and that elevated AnxA6 levels cause LE cholesterol accumulation, we propose that AnxA6 and blockage of LE cholesterol transport are critical for endosomal function required for Stx6-mediated recycling of integrins in cell migration.

show abstract

Section: Discussionmentioning

confidence: 80%

Annexin A6 and Late Endosomal Cholesterol Modulate Integrin Recycling and Cell Migration

García-Melero

Reverter

Hoque

et al. 2016

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…This differential choice between neighbors is probably most relevant to the repair of individual cell death in compact parenchymas such as kidneys and liver, 39,40 which does not involve epithelial-to-mesenchymal transition. We suggest that, in these organs, any of the polarized epithelial cells adjacent to an apoptotic body could react via ZONAB reexpression to replace the expelled apoptotic body by cell division and then redifferentiate.…”

Section: Discussionmentioning

confidence: 99%

ZONAB Promotes Proliferation and Represses Differentiation of Proximal Tubule Epithelial Cells

Lima

Parreira

Devuyst

et al. 2010

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Epithelial polarization modulates gene expression. The transcription factor zonula occludens 1 (ZO-1)-associated nucleic acid binding protein (ZONAB) can shuttle between tight junctions and nuclei, promoting cell proliferation and expression of cyclin D1 and proliferating cell nuclear antigen (PCNA), but whether it also represses epithelial differentiation is unknown. Here, during mouse kidney ontogeny and polarization of proximal tubular cells (OK cells), ZONAB and PCNA levels decreased in parallel and inversely correlated with increasing apical differentiation, reflected by expression of megalin/cubilin, maturation of the brush border, and extension of the primary cilium. Conversely, ZONAB reexpression and loss of apical differentiation markers provided a signature for renal clear cell carcinoma. In confluent OK cells, ZONAB overexpression increased proliferation and PCNA while repressing megalin/cubilin expression and impairing differentiation of the brush border and primary cilium. Reporter and chromatin immunoprecipitation assays demonstrated that megalin and cubilin are ZONAB target genes. Sparsely plated OK cells formed small islands composed of distinct populations: Cells on the periphery, which lacked external tight junctions, strongly expressed nuclear ZONAB, proliferated, and failed to differentiate; central cells, surrounded by continuous junctions, lost nuclear ZONAB, stopped proliferating, and engaged in apical differentiation. Taken together, these data suggest that ZONAB is an important component of the mechanisms that sense epithelial density and participates in the complex transcriptional networks that regulate the switch between proliferation and differentiation.

show abstract

“…One of the well-known effects of TGF-␤ signaling is a dramatic change of the integrin expression profile and as a result, altered cell adhesiveness and migration (Heino et al, 1989;Stamatoglou et al, 1992;Zambruno et al, 1995;Nejjari et al, 1999;Bates et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Transforming Growth Factor β Controls the Directional Migration of Hepatocyte Cohorts by Modulating Their Adhesion to Fibronectin

Binamé

Lassus

Hibner

2008

MBoC

View full text Add to dashboard Cite

Transforming growth factor ␤ (TGF-␤) has a strong impact on liver development and physiopathology, exercised through its pleiotropic effects on growth, differentiation, survival, and migration. When exposed to TGF-␤, the mhAT3F cells, immortalized, highly differentiated hepatocytes, maintained their epithelial morphology and underwent dramatic alterations of adhesion, leading to partial or complete detachment from a culture plate, followed by readhesion and spreading. These alterations of adhesive behavior were caused by sequential changes in expression of the ␣5␤1 integrin and of its ligand, the fibronectin. The altered specificity of anchorage to the extracellular matrix gave rise to changes in cells' collective motility: cohorts adhering to fibronectin maintained a persistent, directional motility, with ezrin-rich pathfinder cells protruding from the tips of the cohorts. The absence of adhesion to fibronectin prevented the appearance of polarized pathfinders and lead to random, oscillatory motility. Our data suggest a novel role for TGF-␤ in the control of collective migration of epithelial cohorts. INTRODUCTIONThe cytokines of the transforming growth factor ␤ (TGF-␤) family have essential and pleiotropic roles in embryonic development, adult homeostasis, and pathology (reviewed in Massague et al., 2000;Bachman and Park, 2005). Although the outcome of the TGF-␤ signaling is strongly dependent on its cross-talk with other signal transduction pathways, as a general rule it is cytostatic and cytotoxic for epithelia and the immune system, while it stimulates differentiation and migration of endothelial and mesenchymal cells (Siegel and Massague, 2003).Liver is one of the organs dramatically affected by the TGF-␤ signaling (reviewed in Bissell et al., 2001). Ectopic expression of the active form of TGF-␤1 gives rise to liver fibrosis through the differentiation of hepatic stellate cells into myofibroblasts and stimulation of collagen synthesis and deposition (Sanderson et al., 1995). During liver regeneration, TGF-␤ acts to control the transient stimulation of stellate cells and, through its growth inhibitory action on hepatocytes, the extent of hepatocyte regenerative proliferation (Romero-Gallo et al., 2005). Primary hepatocytes in culture are also sensitive to TGF-␤: in this setting the cytokine provokes a strong apoptotic response of both mature and fetal hepatocytes (Fabregat et al., 1996;Gressner et al., 1997), whereas early hepatic precursors survive the same treatment . The resistance to the apoptotic effects of TGF-␤ signaling can be achieved by simultaneous activation of MAPK Erk and PI3K survival signaling (Fabregat et al., 1996;Janda et al., 2002;Valdes et al., 2004), which likely accounts for continued survival and proliferation of many hepatoma cell lines in the presence of TGF-␤ (Gressner et al., 1997). Cross-talk with other signal transduction pathways (Janda et al., 2002;Cordenonsi et al., 2003;Kamaraju and Roberts, 2005;Mishra et al., 2005;Katuri et al., 2006), acquisition of mutations invalidati...

show abstract

Temporal changes in the expression and distribution of adhesion molecules during liver development and regeneration.

Cited by 58 publications

References 44 publications

Annexin A6 and Late Endosomal Cholesterol Modulate Integrin Recycling and Cell Migration

Annexin A6 and Late Endosomal Cholesterol Modulate Integrin Recycling and Cell Migration

ZONAB Promotes Proliferation and Represses Differentiation of Proximal Tubule Epithelial Cells

Transforming Growth Factor β Controls the Directional Migration of Hepatocyte Cohorts by Modulating Their Adhesion to Fibronectin

Contact Info

Product

Resources

About