Loss of p120-catenin induces metastatic progression of breast cancer by inducing anoikis resistance and augmenting growth factor receptor signaling

Ron C.J. Schackmann, Sjoerd Klarenbeek, Eva J. Vlug, Suzan Stelloo, Miranda Van Amersfoort, Milou Tenhagen, Tanya M. Braumuller, Jeroen F. Vermeulen, Petra Van Der Groep, Ton Peeters, Elsken Van Der Wall, Paul J. Van Diest, Jos Jonkers, Patrick W.B. Derksen

Research output: Contribution to journalArticle

Abstract

Metastatic breast cancer remains the chief cause of cancer-related death among women in the Western world. Although loss of cell-cell adhesion is key to breast cancer progression, little is known about the underlying mechanisms that drive tumor invasion and metastasis. Here, we show that somatic loss of p120- catenin (p120) in a conditional mouse model of noninvasive mammary carcinoma results in formation of stromal-dense tumors that resemble human metaplastic breast cancer and metastasize to lungs and lymph nodes. Loss of p120 in anchorage-dependent breast cancer cell lines strongly promoted anoikis resistance through hypersensitization of growth factor receptor (GFR) signaling. Interestingly, p120 deletion also induced secretion of inflammatory cytokines, a feature that likely underlies the formation of the prometastatic microenvironment in p120-negative mammary carcinomas. Our results establish a preclinical platform to develop tailored intervention regimens that target GFR signals to treat p120-negative metastatic breast cancers.

Original languageEnglish (US)
Pages (from-to)4937-4949
Number of pages13
JournalCancer Research
Volume73
Issue number15
DOIs
StatePublished - Aug 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Schackmann, R. C. J., Klarenbeek, S., Vlug, E. J., Stelloo, S., Van Amersfoort, M., Tenhagen, M., Braumuller, T. M., Vermeulen, J. F., Van Der Groep, P., Peeters, T., Van Der Wall, E., Van Diest, P. J., Jonkers, J., & Derksen, P. W. B. (2013). Loss of p120-catenin induces metastatic progression of breast cancer by inducing anoikis resistance and augmenting growth factor receptor signaling. Cancer Research, 73(15), 4937-4949. https://doi.org/10.1158/0008-5472.CAN-13-0180