Open AccessCDK4 regulates cancer stemness and is a novel therapeutic target for triple-negative breast cancer
Author(s) -
Meiou Dai,
Chenjing Zhang,
Ayad Mohammed Ali,
Xinyuan Hong,
Jun Tian,
Chieh Lo,
Nadège Fils-Aimé,
Sergio A. Burgos,
Suhad Ali,
Jean-Jacques Lebrun
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep35383
Subject(s) - triple negative breast cancer , breast cancer , cancer research , cancer , medicine , cancer stem cell , ca15 3 , cyclin dependent kinase 4 , stem cell , oncology , biology , cell cycle , cyclin dependent kinase 2 , genetics
Triple negative breast cancers exhibit very aggressive features and poor patient outcomes. These tumors are enriched in cancer stem cells and exhibit resistance to most treatments and chemotherapy. In this study, we found the cyclin-dependent kinase (CDK4) to act as a cancer stem cell regulator and novel prognostic marker in triple negative breast cancers. We found CDK4 to be highly expressed in these tumors and its expression to correlate with poor overall and relapse free survival outcomes, high tumor grade and poor prognostic features of triple negative breast cancer patients. Moreover, we found that blocking CDK4 expression or kinase activity, using a pharmacological inhibitor prevented breast cancer stem cell self-renewal. Interestingly, suppression of CDK4 expression or kinase activity reversed the basal-B TNBC mesenchymal phenotype to an epithelial- and luminal-like phenotype which correlates with better clinical prognosis. Finally, blocking CDK4 activity efficiently eliminated both normal and chemotherapy-resistant cancer cells in triple negative breast cancers, highlighting CDK4 as a promising novel therapeutic target for these aggressive breast tumors.