HOXA1 Is Required for E-cadherin-dependent Anchorage-independent Survival of Human Mammary Carcinoma Cells

Xin Zhang, B. Starling Emerald, Svetlana Mukhina, Kumarasamypet M. Mohankumar, Astrid Kraemer, Alpha S. Yap, Peter D. Gluckman, Kok-Onn Lee, Peter E. Lobie
2005 Journal of Biological Chemistry  
Forced expression of HOXA1 is sufficient to stimulate oncogenic transformation of immortalized human mammary epithelial cells and subsequent tumor formation. We report here that the expression and transcriptional activity of HOXA1 are increased in mammary carcinoma cells at full confluence. This confluence-dependent expression of HOXA1 was abrogated by incubation of cells with EGTA to produce loss of intercellular contact and rescued by extracellular addition of Ca 2؉ . Increased HOXA1
more » ... ased HOXA1 expression at full confluence was prevented by an E-cadherin function-blocking antibody and attachment of non-confluent cells to a substrate by homophilic ligation of E-cadherin increased HOXA1 expression. E-cadherindirected signaling increased HOXA1 expression through Rac1. Increased HOXA1 expression consequent to E-cadherin-activated signaling decreased apoptotic cell death and was required for E-cadherin-dependent anchorage-independent proliferation of human mammary carcinoma cells. HOXA1 is therefore a downstream effector of E-cadherin-directed signaling required for anchorageindependent proliferation of mammary carcinoma cells.
doi:10.1074/jbc.m512666200 pmid:16373333 fatcat:uvr5d7m34bel5jud6jelt56y5q