Formation of E-Cadherin/β-Catenin–based Adherens Junctions in Hepatocytes Requires Serine-10 in p27(Kip1)

Abstract

The adhesion between epithelial cells at adherens junctions is regulated by signaling pathways that mediate the intracellular trafficking and assembly of its core components. Insight into the molecular mechanisms of this is necessary to understand how adherens junctions contribute to the functional organization of epithelial tissues. Here, we demonstrate that in human hepatic HepG2 cells, oncostatin M-p42/44 mitogen-activated protein kinase signaling stimulates the phosphorylation of p27(Kip1) on Ser-10 and promotes cell-cell adhesion. The overexpression of wild-type p27 or a phospho-mimetic p27S10D mutant in HepG2 cells induces a hyper-adhesive phenotype. In contrast, the overexpression of a nonphosphorylatable p27S10A mutant prevents the mobilization of E-cadherin and ␤-catenin at the cell surface, reduces basal cell-cell adhesion strength, and prevents the stimulatory effect of oncostatin M on cell-cell adhesion. As part of the underlying molecular mechanism, it is shown that in p27S10A-expressing cells ␤-catenin interacts with p27 and is prevented from interacting with E-cadherin. The intracellular retention of E-cadherin and ␤-catenin is also observed in hepatocytes from p27S10A knockin mice that express the p27S10A mutant instead of wild-type p27. Together, these data suggest that the formation of adherens junctions in hepatocytes requires Ser-10 in p27.

Fluxes of Ca 2+ and K + Are Required for the Listeriolysin O-Dependent Internalization Pathway of Listeria monocytogenes

“…4B). We also observed a decrease in the internalization of the LLO-deficient strain in Ca 2ϩ -free medium, which was not surprising given the importance of Ca 2ϩ for interaction of the L. monocytogenes invasin InlA with its host cell receptor expressed on HepG2 cells, E-cadherin (16,45,46). Importantly, when comparing internalization in Ca 2ϩ -free medium, there was no longer a significant difference between the internalization of the wt and LLO-deficient strains, demonstrating that an influx of extracellular Ca 2ϩ is required for the LLO-dependent internalization pathway (Fig.…”

ALCAM shedding at the invasive front of the tumor is a marker of myometrial infiltration and promotes invasion in endometrioid endometrial cancer

“…The principal components of adherens junctions in epithelial cells are E-cadherin and β-catenin. E-cadherin is a calcium-dependent transmembrane receptor that interacts homotypically to the E-cadherin of adjacent cells and heterotypically to cytoplasmic-binding proteins, including β-catenin, to transduce external signals within the cell and provide a physical link to the cytoskeleton [ 40 ]. Loss of epithelial polarity and decreased E-cadherin lead to EMT, they have been described to promote invasion and are related to poor prognosis and high-grade EC tumors [ 41 ].…”

E–N-cadherin heterodimers define novel adherens junctions connecting endoderm-derived cells

“…Apparently, a remarkable level of promiscuity of different cadherins is tolerated in some of the endoderm-derived cell types and functions (e.g., Niessen and Gumbiner, 2002 ; Capaldo and Macara, 2007 ; Kan et al, 2007 ). On the one hand, the lack of E-cadherin, for example in hepatocytes and intestinal cells, or its complete exchange by N-cadherin has been found to interfere with specific functions and morphogenic processes and may even result in pathogenic developments (e.g., Théard et al, 2007 , 2008 ; Libusova et al, 2010 ). Our study now suggests that the formations, maintenance, and functions of E–N heterodimer AJs may define a special epithelial differentiation pathway of normal development as well as in tumor formation and progression.…”