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  • β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer.

β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer.

International journal of molecular sciences (2016-09-03)
Hsin-Ling Yin, Chun-Chieh Wu, Chih-Hung Lin, Chee-Yin Chai, Ming-Feng Hou, Shu-Jyuan Chang, Hung-Pei Tsai, Wen-Chun Hung, Mei-Ren Pan, Chi-Wen Luo
ABSTRACT

Triple negative breast cancer (TNBC) displays higher risk of recurrence and distant metastasis. Due to absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), TNBC lacks clinically established targeted therapies. Therefore, understanding of the mechanism underlying the aggressive behaviors of TNBC is required for the design of individualized strategies and the elongation of overall survival duration. Here, we supported a positive correlation between β1 integrin and malignant behaviors such as cell migration, invasion, and drug resistance. We found that silencing of β1 integrin inhibited cell migration, invasion, and increased the sensitivity to anti-cancer drug. In contrast, activation of β1 integrin increased cell migration, invasion, and decreased the sensitivity to anti-cancer drug. Furthermore, we found that silencing of β1 integrin abolished Focal adhesion kinese (FAK) mediated cell survival. Overexpression of FAK could restore cisplatin-induced apoptosis in β1 integrin-depleted cells. Consistent to in vitro data, β1 integrin expression was also positively correlated with FAK (p = 0.031) in clinical tissue. More importantly, β1 integrin expression was significantly correlated with patient outcome. In summary, our study indicated that β1 integrin could regulate TNBC cells migration, invasion, drug sensitivity, and be a potential prognostic biomarker in TNBC patient survival.