p120catenin alteration in cancer and its role in tumour invasion

Abstract

Since its discovery in 1989 as a substrate of the Src oncogene, p120catenin has been revealed as an important player in cancer initiation and tumour dissemination. p120catenin regulates a wide range of cellular processes such as cell–cell adhesion, cell polarity and cell proliferation and plays a pivotal role in morphogenesis, inflammation and innate immunity. The pleiotropic effects of p120catenin rely on its interactions with numerous partners such as classical cadherins at the plasma membrane, Rho-GTPases and microtubules in the cytosol and transcriptional modulators in the nucleus. Alterations of p120catenin in cancer not only concern its expression level but also its intracellular localization and can lead to both pro-invasive and anti-invasive effects. This review focuses on the p120catenin-mediated pathways involved in cell migration and invasion and discusses the potential consequences of major cancer-related p120catenin alterations with respect to tumour spread.

N-cadherin-Presented Slit Repulsive-Cues Direct Collective Schwann cell Migration

“…2f). Consistent with the role of p120-catenin in regulating cadherin levels at the cell-surface 30,[34][35][36] , we found a strong decrease in the levels of N-cadherin at the cell surface, although this was still concentrated at cell-cell contacts, and this was greater in cells treated with the more efficient siRNA2, making it likely that a decrease in N-cadherin at the cell-surface was responsible for the small effect on CIL ( and Supplementary Fig. 2e).…”

“…While the repulsion signal is independent of the trans-homodimerisation of N-cadherin, it remained a possibility that the classical adhesion molecules associated with N-cadherin were required for the CIL signal. We therefore tested whether -catenin and p120-catenin, which are known to physically connect N-cadherin to the actin cytoskeleton and regulate the stability of Ncadherin at the cell-surface respectively, are required for CIL [28][29][30][31][32][33] . Time-lapse microscopy showed that efficient knockdown of -catenin in SCs ( Supplementary Fig.…”

p120ctn-Mediated Organ Patterning Precedes and Determines Pancreatic Progenitor Fate

“…p120ctn is an Armadillodomain protein that functions as a master regulator of adherens junction (AJ) stability by binding to cadherins (Ireton et al, 2002) in addition to regulating the small Rho-GTPases (Noren et al, 2000). p120ctn has been implicated in regulation of migration and cell sorting in cancer and development (McCrea and Park, 2007;Peglion and Etienne-Manneville, 2013), including in the pancreas (Hamada et al, 2013;Hendley et al, 2016). Complete loss of the p120ctn coding gene Ctnnd1 during pancreatic development interferes with branching and acinar differentiation (Hendley et al, 2015).…”

Divergent roles of p120‐catenin isoforms linked to altered cell viability, proliferation, and invasiveness in carcinogen‐induced rat skin tumors

“…We postulated that, rather than Ctnnb1 mutation leading to β‐catenin protein stabilization, a key driver of skin tumorigenesis in the PhIP model might be the deregulation of AJ at the cell periphery, releasing β‐catenin and p120‐catenin to become active in other subcellular compartments . It is known that p120‐catenin binds to the juxtamembrane domain of E‐cadherin and stabilizes diverse cadherins at the cell membrane .…”

“…15,18,37 We postulated that, rather than Ctnnb1 mutation leading to βcatenin protein stabilization, a key driver of skin tumorigenesis in the PhIP model might be the deregulation of AJ at the cell periphery, releasing β-catenin and p120-catenin to become active in other subcellular compartments. [38][39][40][41][42][43][44] It is known that p120-catenin binds to FIGURE 6 Effects of p120-catenin isoforms in human epidermoid carcinoma cells. (A) Transient transfection increased the levels of p120catenin isoforms 1A and 4A (hatched boxes).…”