The role of Axl in drug resistance and epithelial-to-mesenchymal transition of non-small cell lung carcinoma.
Axl, a member of receptor tyrosine kinases (RTKs), has been established as a strong candidate for targeted therapy of cancer. Some reports showed that Axl is a promising therapeutic target to enhance EGFR TKI response in selected EGFR WT NSCLC patients. The present study was aimed to investigate the role of Axl in non-small cell lung carcinoma (NSCLC) drug resistance and the progress of epithelial-to-mesenchymal transition (EMT). MTT was used to detect the cytotoxicity of chemotherapeutic drugs in NSCLC cells, and Western blot to detect the expression of Axl in EGFR wild type NSCLC cell lines. The EMT markers were also determined by Western blot. We found that when downregulating Axl in EGFR WT NSCLC cells, the cells showed a more sensitive response to erlotinib than those overexpressed Axl. The further study showed that when downregulating Axl, the EMT markers E-cadherin was increased while N-cadherin and vimentin were decreased. Those data showed that the inhibition of Axl could reverse the EMT. Combined therapeutic strategies of the inhibitor of Axl and EGFR TKI could be more effective in the treatment of NSCLC drug resistance patients. The EMT signature and Axl might be predictive biomarkers of drug response and therapeutic targets in patients with NSCLC.
Department of Oncology, The First Affiliated Hospital of Nanchang University Nan Chang 330006, China.
Fang
F
Wu
Department of Oncology, The First Affiliated Hospital of Nanchang University Nan Chang 330006, China.
Junhe
J
Li
Department of Oncology, The First Affiliated Hospital of Nanchang University Nan Chang 330006, China.
Changchen
C
Jang
Department of Oncology, The First Affiliated Hospital of Nanchang University Nan Chang 330006, China.
Janfeng
J
Wang
Department of Oncology, The First Affiliated Hospital of Nanchang University Nan Chang 330006, China.
Jianping
J
Xiong
D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015820:Cadherins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011799:Quinazolines / Q000494:pharmacology*; D034622:RNA Interference; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D014746:Vimentin / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase
D015703:Antigens, CD; D000970:Antineoplastic Agents; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011799:Quinazolines; D014746:Vimentin; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
Axl; E-cadherin; EMT; MDR; N-cadherin; vimentin