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整合素α6促进食管癌转移,且是miR-92b的作用靶点。

Integrin α6 promotes esophageal cancer metastasis and is targeted by miR-92b.

作者信息

Ma Gang, Jing Chao, Huang Furong, Li Xukun, Cao Xiufeng, Liu Zhihua

机构信息

The State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Collaborative Innovation Center for Cancer Medicine, Beijing, China.

Department of Oncological Surgery, The Affiliated Nanjing 1st Hospital, Nanjing Medical University, Nanjing, China.

出版信息

Oncotarget. 2017 Jan 24;8(4):6681-6690. doi: 10.18632/oncotarget.14259.

Abstract

Tumor invasion and metastasis is responsible for the poor prognosis of esophageal squamous cell carcinoma (ESCC); therefore, exploring the mechanisms by which malignant cells disseminate, spread and flourish in secondary sites, as well as translating the bench results to clinical practice are in urgent need. Previous reports showed that integrin α6 increases in ESCC specimens and its dysregulated spatial localization correlates positively with the unfavorable outcome of ESCC patients. Here, we clarify that integrin α6 promotes invasion and metastasis of ESCC cells In vitro and in vivo. Mechanistically, decreased integrin α6 attenuates motility of malignant cells partially through deactivating Akt pathway, which is essential for ESCC cells motility. Moreover, integrin α6 serves as a genuine target of miR-92b in suppressing ESCC motility. Our results for the first time describe that miR-92b/integrin α6/Akt axis controls the motility of ESCC, thereby providing a promising diagnosis or therapeutic option.

摘要

肿瘤侵袭和转移是导致食管鳞状细胞癌(ESCC)预后不良的原因;因此,迫切需要探索恶性细胞在继发部位扩散、传播和增殖的机制,并将实验室研究结果转化为临床实践。先前的报道显示,整合素α6在ESCC标本中增加,其失调的空间定位与ESCC患者的不良预后呈正相关。在此,我们阐明整合素α6在体外和体内均促进ESCC细胞的侵袭和转移。机制上,整合素α6的减少部分通过使Akt通路失活来减弱恶性细胞的运动性,而Akt通路对ESCC细胞的运动性至关重要。此外,整合素α6作为miR-92b抑制ESCC运动性的真正靶点。我们的结果首次描述了miR-92b/整合素α6/Akt轴控制ESCC的运动性,从而提供了一种有前景的诊断或治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b23/5351662/41554a818bc8/oncotarget-08-6681-g001.jpg

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