Sci. STKE, 6 March 2001
Cancer Loss of α-Catenin Leads to Hyperproliferation
α-Catenin is one of the intracellular proteins involved in the formation of adherens junctions between epithelial cells. Vasloukhin et al. assessed the consequences of conditional knock out of the α-catenin gene in mouse skin and oral epithelia. Although the mutated epithelial cells expressed proteins associated with normal differentiation, they exhibit a hyperproliferative phenotype very similar to that seen in a precancerous condition called squamous cell carcinoma. The knockout cells showed enhanced phosphorylation of the mitogen-activated protein kinases (MAPKs), ERK1 and ERK2. Knockout cells in culture exhibited an enhanced response to insulin, and removal of insulin from the growth medium eliminated the growth differences between knockout cells and wild-type cells. The mechanism underlying the increased insulin responsiveness in the absence of α-catenin appeared to involve the association of the insulin receptor substrate-1 (IRS-1) with E-cadherin, a transmembrane protein that normally functions as part of the adherins junction and which indirectly interacts with α-catenin through β-catenin.
V. Vasloukhin, C. Bauer, L. Degenstein, B. Wise, E. Fuchs, Hyperproliferation and defects in epithelial polarity upon conditional ablation of α-catenin in skin. Cell 104, 605-617 (2001). [Online Journal]
Citation: Loss of α-Catenin Leads to Hyperproliferation. Sci. STKE 2001, tw9 (2001).
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