title: Overexpression of KAI1 induces autophagy and increases MiaPaCa-2 cell survival through the phosphorylation of extracellular signal-regulated kinases.
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.
authors.affiliation: State Key Laboratory of Cancer Biology and Institute of Digestive Diseases, Xijing Hospital of Digestive Disease, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Yan
authors.forename: Yue-Feng
authors.initials: YF
authors.lastname: Yang
authors.forename: Feng-Jun
authors.initials: FJ
authors.lastname: Xiao
authors.forename: Qing-Fang
authors.initials: QF
authors.lastname: Li
authors.forename: Qun-Wei
authors.initials: QW
authors.lastname: Zhang
authors.forename: Li-Sheng
authors.initials: LS
authors.lastname: Wang
authors.forename: Xiao-Zhong
authors.initials: XZ
authors.lastname: Guo
authors.forename: Hua
authors.initials: H
authors.lastname: Wang
mesh_terms: D001343:Autophagy; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D051861:Kangai-1 Protein / Q000096:biosynthesis* / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000628:therapy; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis; D050796:STAT3 Transcription Factor / Q000378:metabolism
chemical_list: C497688:CD82 protein, human; D051861:Kangai-1 Protein; D050796:STAT3 Transcription Factor; D011065:Poly(ADP-ribose) Polymerases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3