Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway

被引:66
作者
Huang, Ren-hong [1 ]
Quan, Ying-jun [1 ]
Chen, Jin-hong [2 ]
Wang, Ting-feng [1 ]
Xu, Ming [1 ]
Ye, Min [1 ]
Yuan, Hao [1 ]
Zhang, Chong-jie [1 ]
Liu, Xiao-jian [3 ]
Min, Zhi-jun [1 ]
机构
[1] Fudan Univ, Pudong Med Ctr, Shanghai Pudong Hosp, Dept Gastroenterol Surg, 2800 Gongwei Rd, Shanghai 201399, Peoples R China
[2] Fudan Univ, Huashan Hosp, Dept Gen Surg, Shanghai, Peoples R China
[3] Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200032, Peoples R China
关键词
Osteopontin; Autophagy; Proliferation; Migration; Invasion; Apoptosis; Colorectal cancer; P38 MAPK pathway; BREAST-CANCER; CARCINOMA-CELLS; INTEGRIN; METASTASIS; GROWTH; PI3K/AKT/MTOR; PROGRESSION; RESISTANCE; EXPRESSION; BLOCKADE;
D O I
10.1159/000471933
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Osteopontin (OPN) is highly expressed in colorectal cancer (CRC) and is associated with disease progression in vivo. High levels of OPN have been demonstrated to predict low survival rates in CRC. Autophagy is a process of self-digestion, which is thought to autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms Methods: HCT116 cell proliferation, apoptosis, and wound healing assay, and transwell chamber invasion assay, respectively. The ratios of proteins LC3-II/LC3-I, P62, and Atg7 were analyzed by Western-blot. Expressions of Beclin-1, Atg4b, Bnip3, and Vps34, both in transcriptional and translational levels, were analyzed and compared to investigate the formation of autophagosomes. Results: The results showed that OPN can promote cell proliferation, migration, and invasion, as well as inhibit cell apoptosis. It was also demonstrated that OPN could inhibit cell autophagy. Further experiments revealed that the inhibitory effect of OPN on autophagy could be reversed by blocking the p38 MAPK pathway in HCT116 cells. Conclusion: OPN is involved in HCT116 cell progression and is capable of inhibiting cell autophagy possibly by activating the p38 MAPK signaling pathway, implying that OPN could be a potential novel molecular therapeutic biomarker in patients with CRC. (C) 2017 The Author(s) Published by S. Karger AG, Basel.
引用
收藏
页码:1851 / 1864
页数:14
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