title: β1 Integrin as a Prognostic and Predictive Marker in Triple-Negative Breast Cancer.
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.
authors: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. fp7081@gmail.com.|Department of Pathology, Faculty of Medicine, Collage of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. fp7081@gmail.com.
authors: Hsin-Ling
authors: HL
authors: Yin
authors: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. lazzz_wu@yahoo.com.tw.
authors: Chun-Chieh
authors: CC
authors: Wu
authors: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. chlathelas@gmail.com.
authors: Chih-Hung
authors: CH
authors: Lin
authors: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. cychai@kmu.edu.tw.|Department of Pathology, Faculty of Medicine, Collage of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. cychai@kmu.edu.tw.|Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. cychai@kmu.edu.tw.
authors: Chee-Yin
authors: CY
authors: Chai
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. mifeho@kmu.edu.tw.|Cancer Center, Kaohsiung Medical University Hospital, 807 Kaohsiung, Taiwan. mifeho@kmu.edu.tw.|Graduate Institute of Clinical Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. mifeho@kmu.edu.tw.
authors: Ming-Feng
authors: MF
authors: Hou
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. binbin4728@hotmail.com.
authors: Shu-Jyuan
authors: SJ
authors: Chang
authors: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. carbugino@gmail.com.
authors: Hung-Pei
authors: HP
authors: Tsai
authors: Cancer Center, Kaohsiung Medical University Hospital, 807 Kaohsiung, Taiwan. hung1228@nhri.org.tw.|National Institute of Cancer Research, National Health Research Institutes, 704 Tainan, Taiwan. hung1228@nhri.org.tw.
authors: Wen-Chun
authors: WC
authors: Hung
authors: Cancer Center, Kaohsiung Medical University Hospital, 807 Kaohsiung, Taiwan. mrpan@cc.kmu.edu.tw.|Graduate Institute of Clinical Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. mrpan@cc.kmu.edu.tw.|Research Center for Environmental Medicine, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. mrpan@cc.kmu.edu.tw.
authors: Mei-Ren
authors: MR
authors: Pan
authors: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, 807 Kaohsiung, Taiwan. 1040141@kmuh.org.tw.|Cancer Center, Kaohsiung Medical University Hospital, 807 Kaohsiung, Taiwan. 1040141@kmuh.org.tw.
authors: Chi-Wen
authors: CW
authors: Luo
mesh_terms: D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D019012:Integrin beta1 / Q000235:genetics / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D019012:Integrin beta1; D051416:Focal Adhesion Protein-Tyrosine Kinases
keywords: Triple negative breast cancer; drug sensitivity; invasion; migration; β1 integrin