Overexpression of KAI1 induces autophagy and increases MiaPaCa-2 cell survival through the phosphorylation of extracellular signal-regulated kinases |
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Authors: | Wu Chun-Yan Yan Jun Yang Yue-Feng Xiao Feng-Jun Li Qing-Fang Zhang Qun-Wei Wang Li-Sheng Guo Xiao-Zhong Wang Hua |
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Institution: | aState Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi’an 710032, PR China;bDepartment of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China;cDepartment of Gastroenterology, Shenyang General Hospital of PLA, 83 Wenhua Road, Shenyang 110016, PR China |
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Abstract: | KAI1, a metastasis-suppressor gene belonging to the tetraspanin family, is known to inhibit cancer metastasis without affecting the primary tumorigenicity by inhibiting the epidermal growth factor (EGF) signaling pathway. Recent studies have shown that hypoxic conditions of solid tumors induce high-level autophagy and KAI1 expression. However, the relationship between autophagy and KAI1 remains unclear. By using transmission electron microscopy, confocal microscopy, and Western blotting, we found that KAI1 can induce autophagy in a dose- and time-dependent manner in the human pancreatic cell line MiaPaCa-2. KAI1-induced autophagy was confirmed by the expression of autophagy-related proteins LC3 and Beclin 1. KAI1 induces autophagy through phosphorylation of extracellular signal-related kinases rather than that of AKT. KAI1-induced autophagy protects MiaPaCa-2 cells from apoptosis and proliferation inhibition partially through the downregulation of poly adenosine diphosphate (ADP)-ribose] polymerase (PARP) cleavage and caspase-3 activation. |
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Keywords: | KAI1 Autophagy Apoptosis Signal pathway |
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