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E-cadherin regulates human Nanos1, which interacts with p120ctn and induces tumor cell migration and invasion.

Abstract : Down-regulation of the epithelial cell-cell adhesion molecule E-cadherin is frequently associated with tumor formation and progression. Besides its role in physical cell-cell adhesion, E-cadherin is also thought to be involved in intracellular signaling in normal epithelial cells. In these cells, the Armadillo catenin p120ctn binds to the cytoplasmic domain of E-cadherin and stabilizes the adhesion complexes. On loss of E-cadherin, cytoplasmic p120ctn might accumulate and contribute to tumor malignancy. We used suppression subtractive hybridization to search for genes regulated by E-cadherin expression. We isolated human Nanos1 as a transcript of which levels decrease on E-cadherin reexpression in a human breast cancer cell line. The hNanos1 protein bears a COOH-terminal (CCHC)(2) zinc finger domain and belongs to an evolutionarily conserved protein family sharing functions in germ cell development in both vertebrates and invertebrates. We found an inverse correlation between E-cadherin and hNanos1 expression in various cell lines and under diverse conditions. Conditional expression of hNanos1 in human colorectal DLD1 cancer cells functionally abolished cell-cell adhesion. It induced cytoplasmic translocation of p120ctn, as well as strong migratory and invasive properties. We also found that the NH(2)-terminal domain of hNanos1, which is conserved only among mammals, interacts with p120ctn. hNanos1 counteracted the stimulatory effect of p120ctn on cell protrusion formation. Together, these findings describe a new function for hNanos1 as a downstream effector of E-cadherin loss contributing to tumor progression. Targeting hNanos1 might be a promising strategy in the treatment of E-cadherin-negative tumors in particular.
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Contributor : Philippe Birembaut <>
Submitted on : Friday, May 4, 2007 - 10:27:51 AM
Last modification on : Wednesday, August 30, 2017 - 1:13:38 AM

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Kristin Strumane, Arnaud Bonnomet, Christophe Stove, Roosmarijn Vandenbroucke, Beatrice Nawrocki-Raby, et al.. E-cadherin regulates human Nanos1, which interacts with p120ctn and induces tumor cell migration and invasion.. Cancer Research, American Association for Cancer Research, 2006, 66 (20), pp.10007-15. ⟨10.1158/0008-5472.CAN-05-3096⟩. ⟨inserm-00144608⟩



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