title: Knockdown of Rap1b Enhances Apoptosis and Autophagy in Gastric Cancer Cells via the PI3K/Akt/mTOR Pathway.
abstract: Gastric cancer (GC) is the fourth most common malignancy and the second leading cause of cancer mortality around the world. However, the regulatory mechanisms of GC tumorigenesis and cancer cell motility are completely unknown. We investigated the role of a RAS-related protein (Rap1b) in the progression of GC. Our results showed that the expression of Rap1b is aberrantly upregulated in GC tissue samples and human GC cell lines, and the high expression of Rap1b indicated a positive correlation with poor prognosis in patients with GC. Inhibition of endogenous Rap1b dramatically reduced the cell cycle progression but strongly enhanced the apoptosis capacity of human GC cell lines MKN-28 and SGC-7901 cells compared with the control group. Western blotting assay showed that Rap1b inhibition resulted in a significant increase in the ratio of LC3-II to LC3-I, and the levels of p62 protein were decreased in both MKN-28 and SGC-7901 cells. Furthermore, PI3K/Akt/mTOR activation was found to be maintained in a low level in the normal gastric mucosal epithelial cells, while it was significantly upregulated in GC cells, which could be decreased by Rap1b inhibition. The PI3K inhibitor LY294002 was enhanced but activator insulin-like growth factor 1 (IGF-1) blocked the Rap1b silencing-induced enhancement of apoptosis and autophagy in MKN-28 and SGC-7901 cells. In conclusion, we demonstrate that Rap1b expression is aberrantly increased in GC, resulting in the inhibition of autophagy and apoptosis of GC cells by the PI3K/Akt/mTOR pathway. This might provide a new understanding and represent a novel therapeutic target for human GC.
authors.affiliation: Department of Interventional Radiology, Hi-Tech People Hospital, BaoJi, China.
authors.forename: Yazhou
authors.initials: Y
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Feiyu
authors.initials: F
authors.lastname: Shi
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Junjun
authors.initials: J
authors.lastname: She
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D008297:Male; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D014162:Transfection; D020668:rap GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020668:rap GTP-Binding Proteins; C546842:MTOR protein, human; C116753:RAP1B protein, human