CIP4 promotes metastasis in triple-negative breast cancer and is associated with poor patient prognosis

Signaling via epidermal growth factor receptor (EGFR) and Src kinase pathways promote triple-negative breast cancer (TNBC) cell invasion and tumor metastasis. Here, we address the role of Cdc42-interacting protein-4 (CIP4) in TNBC metastasis in vivo, and profile CIP4 expression in human breast cance...

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Bibliographic Details
Published in:Oncotarget 2015-04, Vol.6 (11), p.9397-9408
Main Authors: Cerqueira, Otto L D, Truesdell, Peter, Baldassarre, Tomas, Vilella-Arias, Santiago A, Watt, Kathleen, Meens, Jalna, Chander, Harish, Osório, Cynthia A B, Soares, Fernando A, Reis, Eduardo M, Craig, Andrew W B
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Animals
Carcinoma, Ductal, Breast - diagnosis
Carcinoma, Ductal, Breast - genetics
Carcinoma, Ductal, Breast - mortality
Carcinoma, Ductal, Breast - pathology
Cell Line, Tumor
Female
Gene Expression Regulation, Neoplastic
Humans
Mice
Mice, Transgenic
Microtubule-Associated Proteins - physiology
Middle Aged
Minor Histocompatibility Antigens
Neoplasm Invasiveness
Neoplasm Metastasis
Prognosis
Rats
Research Paper
Triple Negative Breast Neoplasms - diagnosis
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - mortality
Triple Negative Breast Neoplasms - pathology
Xenograft Model Antitumor Assays
Young Adult
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Summary:Signaling via epidermal growth factor receptor (EGFR) and Src kinase pathways promote triple-negative breast cancer (TNBC) cell invasion and tumor metastasis. Here, we address the role of Cdc42-interacting protein-4 (CIP4) in TNBC metastasis in vivo, and profile CIP4 expression in human breast cancer patients. In human TNBC cells, CIP4 knock-down (KD) led to less sustained activation of Erk kinase and impaired cell motility compared to control cells. This correlated with significant defects in 3D invasion of surrounding extracellular matrix by CIP4 KD TNBC cells when grown as spheroid colonies. In mammary orthotopic xenograft assays using both human TNBC cells (MDA-MB-231, HCC 1806) and rat MTLn3 cells, CIP4 silencing had no overt effect on tumor growth, but significantly reduced the incidence of lung metastases in each tumor model. In human invasive breast cancers, high CIP4 levels was significantly associated with high tumor stage, TNBC and HER2 subtypes, and risk of progression to metastatic disease. Together, these results implicate CIP4 in promoting metastasis in TNBCs.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.3351