TY - JOUR
T1 - Loss of p120-catenin induces metastatic progression of breast cancer by inducing anoikis resistance and augmenting growth factor receptor signaling
AU - Schackmann, Ron C.J.
AU - Klarenbeek, Sjoerd
AU - Vlug, Eva J.
AU - Stelloo, Suzan
AU - Van Amersfoort, Miranda
AU - Tenhagen, Milou
AU - Braumuller, Tanya M.
AU - Vermeulen, Jeroen F.
AU - Van Der Groep, Petra
AU - Peeters, Ton
AU - Van Der Wall, Elsken
AU - Van Diest, Paul J.
AU - Jonkers, Jos
AU - Derksen, Patrick W.B.
PY - 2013/8/1
Y1 - 2013/8/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84881416716&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-13-0180
DO - 10.1158/0008-5472.CAN-13-0180
M3 - Article
C2 - 23733751
AN - SCOPUS:84881416716
SN - 0008-5472
VL - 73
SP - 4937
EP - 4949
JO - Cancer Research
JF - Cancer Research
IS - 15
ER -