title: Gas6/Axl mediates tumor cell apoptosis, migration and invasion and predicts the clinical outcome of osteosarcoma patients.
abstract: Dysregulation of the receptor tyrosine kinase Axl and its ligand Gas6 has been shown to promote multiple tumorigenic processes, as well as to correlate with worse prognosis in many different tumor types. However, studies of Axl expression and function in osteosarcoma have rarely been reported. In this study, we report that activated Axl is highly expressed in osteosarcoma cells, and this expression is significantly correlated with the recurrence and lung metastasis of osteosarcoma patients. High expression of activated Axl was an independent predictor for worse prognosis in osteosarcoma. Additionally, we confirmed a strong positive correlation between P-Axl and MMP-9 expression in those osteosarcoma patients. In osteosarcoma cell lines MG63 and U2OS, 200 ng/ml rhGas6 could cause obvious increase of P-Axl expression within 30 min, consistent with the expression of P-AKT. In both of the cell lines, Axl activated by rhGas6 could protect the tumor cells from apoptosis caused by serum starvation, and promote tumor cells' migration and invasion in vitro. Together with previous data, these studies suggest that activated Axl participate in the progression of osteosarcoma by resisting tumor cells apoptosis and promoting their migration and invasion, which may be linked to the expression of MMP-9. In the mechanism, AKT signaling pathway may contribute to the function of P-Axl in osteosarcoma rather than ERK pathway.
authors.affiliation: 1st Affiliated Hospital of Sun Yat-sen University, Pathology Department, Guangzhou 510080, PR China. christina_531@163.com
authors.forename: Ju
authors.initials: J
authors.lastname: Han
authors.forename: Rui
authors.initials: R
authors.lastname: Tian
authors.forename: Bicheng
authors.initials: B
authors.lastname: Yong
authors.forename: Canqiao
authors.initials: C
authors.lastname: Luo
authors.forename: Pingxian
authors.initials: P
authors.lastname: Tan
authors.forename: Jingnan
authors.initials: J
authors.lastname: Shen
authors.forename: Tingsheng
authors.initials: T
authors.lastname: Peng
mesh_terms: D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002648:Child; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D055815:Young Adult; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D020780:Matrix Metalloproteinase 9; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C579270:MMP9 protein, human; C000722289:AXL protein, human