@Article{096504021X16203818567367,
AUTHOR = {Weili Min, Liangzhang Sun, Burong Li, Xiao Gao, Shuqun Zhang, Yang Zhao},
TITLE = {lncCRLA Enhanced Chemoresistance in Lung Adenocarcinoma  That Underwent Epithelial–Mesenchymal Transition},
JOURNAL = {Oncology Research},
VOLUME = {28},
YEAR = {2020},
NUMBER = {9},
PAGES = {857--872},
URL = {http://www.techscience.com/or/v28n9/48481},
ISSN = {1555-3906},
ABSTRACT = {EMT confers increased metastatic potential and the resistance to chemotherapies to cancer cells. However, the 
precise mechanisms of EMT-related chemotherapy resistance remain unclear. c-Src-mediated caspase 8 phosphorylation essential for EMT in lung adenocarcinoma cell lines preferentially occurs in cells with the mesenchymal phenotype, resulting in chemoresistance to cisplatin plus paclitaxel in patients with resectable lung 
adenocarcinoma and a significantly worse 5-year PFS. Cisplatin killed lung adenocarcinoma cells regardless of 
caspase 8. Paclitaxel-triggered necroptosis in lung adenocarcinoma cells was dependent on the phosphorylation 
or deficiency of caspase 8, during which FADD interacted with RIPK1 to activate the RIPK1/RIPK3/MLKL 
signaling axis. Accompanied with c-Src-mediated caspase 8 phosphorylation to trigger EMT, a novel lncRNA 
named lncCRLA was markedly upregulated and inhibited RIPK1-induced necroptosis by impairing RIPK1–
RIPK3 interaction via binding to the intermediate domain of RIPK1. Dasatinib mitigated c-Src-mediated phosphorylation of caspase 8-induced EMT and enhanced necroptosis in mesenchymal-like lung adenocarcinoma 
cells treated with paclitaxel, while c-FLIP knockdown predominantly sensitized the mesenchymal-like lung 
adenocarcinoma cells to paclitaxel + dasatinib. c-Src–caspase 8 interaction initiates EMT and chemoresistance 
via caspase 8 phosphorylation and lncCRLA expression, to which the dasatinib/paclitaxel liposome + siFLIP 
regimen was lethal.},
DOI = {10.3727/096504021X16203818567367}
}