1. Missing-in-metastasis B (MIM-B) combined with caveolin-1 promotes metastasis of hepatocellular carcinoma
- Author
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Zhenqian Wu, Zhao-You Tang, Xiu-Yan Huang, Zi-Li Huang, Qi Zheng, Tao Niu, Zi Chen, Bin Xu, Yong-Hua Xu, Jian Zhou, and Xinyu Huang
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pathology ,congenital, hereditary, and neonatal diseases and abnormalities ,caveolin-1 ,Cell ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,otorhinolaryngologic diseases ,metastasis ,Epidermal growth factor receptor ,biology ,business.industry ,Cancer ,hepatocellular carcinoma ,medicine.disease ,missing in metastasis B ,digestive system diseases ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Caveolin 1 ,biology.protein ,Immunohistochemistry ,Liver cancer ,business ,epidermal growth factor receptor ,Research Paper - Abstract
// Xiu-Yan Huang 1, * , Zi-Li Huang 2, * , Tao Niu 3, * , Zhen-Qian Wu 1, * , Bin Xu 4, * , Yong-Hua Xu 2 , Xin-Yu Huang 1 , Qi Zheng 1 , Jian Zhou 5 , Zi Chen 6 and Zhao-You Tang 5 1 Department of General Surgery, Shanghai Jiaotong University Affiliated Sixth People’s Hospital, Shanghai, P.R. China 2 Department of Radiology, Xuhui Central Hospital, Shanghai, P.R. China 3 Department of General Surgery, People’s Hospital of Menghai County, Yunnan Province, P.R. China 4 Department of General Surgery, The Tenth People’s Hospital of Tongji University, Shanghai, P.R. China 5 Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, P.R. China 6 Thayer School of Engineering, Norris Cotton Cancer Center, Dartmouth College, Hanover, NH, USA * These authors have contributed equally to this work Correspondence to: Xiu-Yan Huang, email: xyhuang1119@163.com Keywords: hepatocellular carcinoma; missing in metastasis B; caveolin-1; epidermal growth factor receptor; metastasis Received: December 14, 2016 Accepted: August 04, 2017 Published: September 08, 2017 ABSTRACT Background: Increasing amounts of evidence indicate that Missing in metastasis B (MIM-B) promotes cancer metastasis. Here, we sought to better understand the mechanism through which MIM-B promotes tumor metastasis in hepatocellular carcinoma (HCC). Methods: We performed confocal microscopy analysis to determine the distributions of MIM-B and caveolin-1 and conducted co-immunoprecipitation assays to detect the interactions between MIM-B and caveolin-1 in vitro . We performed transwell assays to analyze the invasive ability of HCC cells. Changes in the expression levels of key genes and some molecular makers were detected by immunohistochemistry and western blotting in HCC tissue samples. Results: We found that MIM-B co-localizes with caveolin-1 and demonstrated that MIM-B and caveolin-1 interact in vitro . Repressing MIM-B and caveolin-1 expression inhibited the epidermal growth factor receptor signaling pathway. We overexpressed MIM-B and caveolin-1 in Hep3B cells, which enhanced Hep3B cell invasiveness. Furthermore, MHCC97H cell invasiveness was significantly decreased in cells in which MIM-B and caveolin-1 expression was inhibited. Additionally, we found that MIM-B and caveolin-1 were expressed at higher levels in HCC tissues than in paired normal tissues. Moreover, HCC patients with MIM-B and caveolin-1 up-regulation experienced significantly worse outcomes than controls ( P < 0.001), and HCC patients with high MIM-B and caveolin-1 expression levels often developed pulmonary metastasis ( P < 0.001). Conclusions: MIM-B combined with caveolin-1 promotes metastasis of HCC, and elevated MIM-B and caveolin-1 expression levels are associated with a poor prognosis in HCC patients; therefore, MIM-B and caveolin-1 may represent novel targets for the diagnosis and treatment of HCC.
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- 2017