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整合素β1是促进食管鳞状细胞癌转移和化疗耐药的关键效应分子。

Integrin β1 is a critical effector in promoting metastasis and chemo-resistance of esophageal squamous cell carcinoma.

作者信息

Xu Zhipeng, Zou Li, Ma Gang, Wu Xiaowei, Huang Furong, Feng Tingting, Li Suqing, Lin Qingfeng, He Xiaoting, Liu Zhihua, Cao Xiufeng

机构信息

Department of Surgical Oncology, Nanjing First Hospital, Nanjing Medical University Nanjing, China.

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.

出版信息

Am J Cancer Res. 2017 Mar 1;7(3):531-542. eCollection 2017.

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, functional 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 on and experiments. 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.

摘要

食管鳞状细胞癌(ESCC)的转移在临床实践中仍然是一个挑战。在本研究中,我们阐明了整合素β1(ITGB1)在ESCC转移中起关键作用。通过分析ESCC标本中整合素β1的表达,我们发现该整合素在恶性组织中的表达高于正常组织,且这种增加与淋巴结转移相关。此外,功能实验表明,整合素β1的缺失损害了ESCC细胞的运动能力,并且我们还表明,整合素β1的缺失显著抑制了两种小鼠模型的肺和淋巴结中的转移形成。机制上,整合素β1通过调节FAK-Rac1信号通路促进细胞运动。最后,基于 和 实验,我们发现阻断整合素β1显著损害了ESCC细胞对顺铂(DDP)治疗的抗性。总体而言,我们的数据表明整合素β1促进转移并赋予ESCC顺铂抗性,这为未来靶向该蛋白治疗ESCC提供了实验证据。

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