title: Integrin β1 is a critical effector in promoting metastasis and chemo-resistance of esophageal squamous cell carcinoma.
abstract: Metastasis of esophageal squamous cell carcinoma (ESCC) remains a challenge in clinical practice. In this study, we clarified that integrin β1 (ITGB1) plays critical roles in the metastasis of ESCC. By analyzing the expression of integrin β1 in ESCC specimens, we found that the expression of this integrin was higher in malignant than in normal tissues and that this increase was associated with lymph node metastasis. Moreover,in vitrofunctional experiments demonstrated that deletion of integrin β1 impaired the motility of ESCC cells, and we also showed that integrin β1 deletion significantly inhibited metastases formation in the lungs and lymph nodes of two murine models. Mechanistically, integrin β1 promoted cellular motility by regulating the FAK-Rac1 signaling pathway. Finally, we found that blocking integrin β1 significantly impaired the resistance of ESCC cells to cisplatin (DDP) treatment based onin vitroandin vivoexperiments. Overall, our data suggest that integrin β1 promotes metastasis and confers DDP resistance to ESCC, which provides experimental evidence for targeting this protein to treat ESCC in the future.
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zou
authors.affiliation: The State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing, China; Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and TherapyTianjin 300060, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ma
authors.affiliation: The State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Wu
authors.affiliation: The State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Furong
authors.initials: F
authors.lastname: Huang
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Suqing
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Lin
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: He
authors.affiliation: The State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Beijing, China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.
authors.forename: Xiufeng
authors.initials: X
authors.lastname: Cao
keywords: FAK; Integrin β1; chemo-resistance; esophageal cancer; metastasis