Open AccessNuclear p120-catenin contributes to anoikis resistance of Lobular Breast Cancer through Kaiso-dependent Wnt11 expression
Author(s) -
Robert A. H. van de Ven,
Milou Tenhagen,
Wouter Meuleman,
Jeske J. G. van Riel,
Ron C.J. Schackmann,
Patrick W.B. Derksen
Publication year - 2015
Publication title -
disease models and mechanisms
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.327
H-Index - 83
eISSN - 1754-8411
pISSN - 1754-8403
DOI - 10.1242/dmm.018648
Subject(s) - anoikis , rhoa , microbiology and biotechnology , downregulation and upregulation , cancer research , catenin , biology , metastasis , signal transduction , cancer , wnt signaling pathway , genetics , gene
E-cadherin inactivation underpins the progression of invasive lobular breast carcinoma (ILC). In ILC, p120-catenin (p120) translocates to the cytosol where it controls anchorage independence through the Rho-Rock signaling pathway, a key mechanism driving tumor growth and metastasis. We now demonstrate that anchorage-independent ILC cells show an increase in nuclear p120, which results in relief of transcriptional repression by Kaiso. To identify the Kaiso target genes that control anchorage independence we performed genome-wide mRNA profiling on anoikis-resistant mouse ILC cells, and identified 29 candidate target genes, including the established Kaiso target Wnt11. Our data indicate that anchorage-independent upregulation of Wnt11 in ILC cells is controlled by nuclear p120 through inhibition of Kaiso-mediated transcriptional repression. Finally, we show that Wnt11 promotes activation of RhoA, which causes ILC anoikis resistance. Our findings thereby establish a mechanistic link between E-cadherin loss and subsequent control of Rho-driven anoikis resistance through p120- and Kaiso-dependent expression of Wnt11.