@Article{096504016X14648701447814,
AUTHOR = {Yaqiong Tian, Zengli Zhang, Liyun Miao, Zhimin Yang, Jie Yang, Yinhua Wang, Danwen Qian, 
Hourong Cai, Yongsheng Wang},
TITLE = {Anexelekto (AXL) Increases Resistance to EGFR-TKI and Activation of AKT  and ERK1/2 in Non-Small Cell Lung Cancer Cells},
JOURNAL = {Oncology Research},
VOLUME = {24},
YEAR = {2016},
NUMBER = {5},
PAGES = {295--303},
URL = {http://www.techscience.com/or/v24n5/56978},
ISSN = {1555-3906},
ABSTRACT = {Recently, epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have revolutionized nonsmall cell lung cancer (NSCLC) treatment. However, resistance remains a major obstacle. Anexelekto (AXL) 
is a member of receptor tyrosine kinases (RTKs) and shares the same downstream signaling pathways with 
EGFR, such as PI3K/AKT and MAPK/ERK. AXL overexpression in resistant tumors has been implicated in 
many previous studies in vitro and in vivo. In this study, we further examined whether expression of AXL and its 
downstream targets increased in gefitinib-resistant PC9 cells (PC9GR). In addition, we hypothesize that knocking down AXL in PC9GR and overexpressing AXL in PC9 using genetic tools can restore and decrease the 
sensitivity to gefitinib, respectively. We found that silencing AXL could sensitize the resistance to gefitinib, and 
the downstream pathways were significantly inhibited. Interestingly, we also discovered that increased AXL 
expression did promote the resistance, and its downstream targets were activated accordingly. Then 69 NSCLC 
patients who harbored EGFR mutation were recruited to analyze the expression of AXL and the association 
between AXL expression and clinical characteristics. We found that 5 of the 69 patients were AXL positive 
(about 7%), and AXL was related to tumor differentiation and tumor size. In this study, we concluded that the 
molecular mechanisms of AXL mediated resistance involved in the increased activity of the PI3K/AKT and 
MAPK/ERK1/2 pathways, and AXL overexpression could promote resistance, but it can be weakened when 
AXL expression is silenced.},
DOI = {10.3727/096504016X14648701447814}
}