title: Osteopontin Promotes Cell Migration and Invasion, and Inhibits Apoptosis and Autophagy in Colorectal Cancer by activating the p38 MAPK Signaling Pathway.
abstract: 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 play a significant role in carcinogenesis. However, the mechanisms of OPN's effects on CRC cell autophagy have not been elucidated. Therefore, we aimed to investigate possible mechanisms of OPN's effects on CRC autophagy.
  
  
  METHODS
  HCT116 cell proliferation, apoptosis, and migration and invasion ability were identified by cell counting k¡t-8 assay, flow cytometry, 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 by RT-PCR and Western blot. Immunofluorescence and co-focusing experiments were used 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Ren-Hong
authors.initials: RH
authors.lastname: Huang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Ying-Jun
authors.initials: YJ
authors.lastname: Quan
authors.affiliation: Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.
authors.forename: Jin-Hong
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Ting-Feng
authors.initials: TF
authors.lastname: Wang
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Ye
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Chong-Jie
authors.initials: CJ
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Shanghai Cancer Center, Fudan University, Shanghai, China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: Department of Gastrointestinal Surgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
authors.forename: Zhi-Jun
authors.initials: ZJ
authors.lastname: Min
mesh_terms: D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D002465:Cell Movement; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D009363:Neoplasm Proteins; C506895:SPP1 protein, human; D053495:Osteopontin; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Apoptosis; Autophagy; Colorectal cancer; Invasion; Migration; Osteopontin; P38 MAPK pathway; Proliferation