title: Axl gene knockdown inhibits the metastasis properties of hepatocellular carcinoma via PI3K/Akt-PAK1 signal pathway.
abstract: The objective of this study is to clarify the possible role and mechanism of Axl in the tumorigenicity and metastasis process of hepatocellular carcinoma. The mRNA and protein expression levels of Axl in MHCC97-H and MHCC97-L cell lines were evaluated by real-time PCR and Western blot analysis. The key factor of phosphatidylinositol-3-kinase (PI3K)/Akt-p21-activated kinases-1 (PAK1) signaling pathway was studied after Axl expression was downregulated by shRNA. Finally, we analyzed the expression status of Axl protein expression in hepatocellular carcinoma tissues and its relationship with the prognosis of hepatocellular carcinoma. Axl was observed to be higher expressed in MHCC97-H cell lines compared to MHCC97-L cell lines. The downregulation of Axl in MHCC97-H cell lines resulted in the inhibition of the invasion ability of MHCC97-H cells both in vitro and in vivo. Interestingly, blocking PI3K/Akt signaling pathway by LY294002 or Akt siRNA could remarkably inhibit the PAK1 activation and cell invasion. Finally, the Axl protein expression was positively correlated with differentiation, lymph node metastasis, and clinical stage in patients with hepatocellular carcinoma patients (all P < 0.01). These findings suggest that Axl can also regulate the metastasis process of hepatocellular carcinoma and may serve as a new prognostic marker and therapeutic target for treating hepatocellular carcinoma metastasis.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, 116027, Liaoning Province, China.
authors.forename: Jingchao
authors.initials: J
authors.lastname: Xu
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.forename: Hongye
authors.initials: H
authors.lastname: Ma
authors.forename: Yanping
authors.initials: Y
authors.lastname: Li
authors.forename: Zhenhai
authors.initials: Z
authors.lastname: Ma
authors.forename: Yongfu
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000556:secondary*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D054462:p21-Activated Kinases / Q000502:physiology*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; C515903:PAK1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D054462:p21-Activated Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human