Differential expression of Axl in hepatocellular carcinoma and correlation with tumor lymphatic metastasis.
Protein kinases play important roles in tumor development and progression. A variety of members of the signal transduction enzymes serve as targets for therapeutic intervention in cancer. The dysregulation of Axl receptor and its ligand growth arrest-specific 6 (Gas6) is implicated in the pathogenesis of several cancers. In this study, the differential expressions of Axl were investigated in mouse hepatocarcinoma cell lines Hca-F and Hca-P, which have high- and low-metastatic potential to lymph nodes. Experimental inhibition of Axl by siRNA assessed further the metastatic potential of Axl. The results showed that down-regulation of Axl expression attenuated Hca-F cells proliferation, migration, and invasion in vitro, as well as inhibited metastasis to peripheral lymph nodes in vivo. Further analysis demonstrated that the addition of exogenous Gas6 mediated the migration and invasion of Hca-F cells both in vitro and in vivo through Axl. Furthermore, Gas6 stimulation of Axl in Hca-F cells resulted primarily in the down-regulation of Cyr61, a member of the CCN protein family involved in tumor progression. These data suggest that Axl acts as a tumor lymphatic metastasis-associated gene, and may function partly through the regulation of Cyr61.
He
Ling
L
College of Laboratory Medicine, Dalian Medical University, Liaoning Province, China.
Zhang
Jianing
J
Jiang
Lili
L
Jin
Changgong
C
Zhao
Yongfu
Y
Yang
Guang
G
Jia
Li
L
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000556:secondary*; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722290:AXL receptor tyrosine kinase, mouse