title: AXL and MET receptor tyrosine kinases are essential for lung cancer metastasis.
abstract: The AXL and MET receptors regulate key processes in tumor growth, metastasis, and drug resistance; thus, they have recently been implicated as promising therapeutic targets in various tumors. We investigated the metastatic potential and crosstalk between these receptors in non‑small cell lung cancer (NSCLC). We found that the treatment of NSCLC cells with hepatocyte growth factor (HGF) and growth arrest-specific 6 (Gas6), as ligands for MET and AXL, respectively, promoted their migration and invasion ability. However, treatment with inhibitors of each of these receptors significantly reduced the migratory and invasiveness of the cells, although their inhibitory rates varied according to the inhibition of each receptor. In addition, the suppression of each receptor by shRNA resulted in reduced migration and invasiveness. Notably, the suppression of AXL was more effective than the suppression of MET in the inhibition of migration and invasion. In accordance with in vitro results, when the cells were transferred via tail vein injection, AXL inhibition was more efficient in attenuating metastasis than MET inhibition. Clinically, AXL or MET expression is associated with a poor prognosis in primary tumors of NSCLC. In summary, AXL and MET can regulate tumor metastasis, but AXL was shown to be more potent than MET in lung metastasis. Thus, we conclude that AXL might be a suitable therapeutic target for the inhibition of lung metastasis.
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Department of Biomedical Sciences, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Asan Institute for Life Sciences, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
authors.forename: Jin Kyung
authors.initials: JK
authors.lastname: Rho
authors.affiliation: Dongnam Institute of Radiological and Medical Sciences (DIRAMS), Busan 619-953, Republic of Korea.
authors.forename: Joong Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
authors.forename: Chang-Min
authors.initials: CM
authors.lastname: Choi
authors.affiliation: Department of Pulmonology and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
authors.forename: Woo Sung
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Biomedical Sciences, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
authors.forename: Jaekyoung
authors.initials: J
authors.lastname: Son
authors.affiliation: Department of Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Republic of Korea.
authors.forename: Jae Cheol
authors.initials: JC
authors.lastname: Lee
mesh_terms: D000072283:A549 Cells; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics* / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D011518:Proto-Oncogene Proteins; D034741:RNA, Small Interfering; D017228:Hepatocyte Growth Factor; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase