EML4-ALK induces epithelial-mesenchymal transition consistent with cancer stem cell properties in H1299 non-small cell lung cancer cells.
The echinoderm microtubule-associated protein-like 4(EML4)--anaplastic lymphoma kinase (ALK) fusion gene has been identified as a driver mutation in non-small-cell lung cancer (NSCLC). However, the role of EML4-ALK in malignant transformation is not entirely clear. Here, for the first time, we showed that H1299 NSCLC cells stably expressing EML4-ALK acquire EMT phenotype, associated with enhanced invasive migration and increased expression of EMT-inducing transcription factors. H1299-EML4-ALK cells also displayed cancer stem cell-like properties with a concomitant up-regulation of CD133 and enhanced ability of mammospheres formation. Moreover, we found that inhibition of ERK1/2 reversed EMT induced by EML4-ALK in H1299 cells. Taken together, these results suggested that EML4-ALK induced ERK activation is mechanistically associated with EMT phenotype. Thus, inhibition of ERK signaling pathway could be a potential strategy in treatment of NSCLC patients with EML4-ALK translocation.
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Fuchun
F
Guo
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: liuxk57@163.com.
Xiaoke
X
Liu
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: qinqingscu@126.com.
Qin
Q
Qing
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: yaxiongsang@gmail.com.
Yaxiong
Y
Sang
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: leymj@163.com.
Chengjun
C
Feng
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: lixiaoyu2012huaxi@163.com.
Xiaoyu
X
Li
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: summer.jl06@foxmail.com.
Li
L
Jiang
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: keyanxiaozhu@163.com.
Pei
P
Su
Department of Thoracic Oncology, Cancer Center, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: wangys@scu.edu.cn.
Yongsheng
Y
Wang
D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002471:Cell Transformation, Neoplastic; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology*; D050596:Oncogene Fusion; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D018874:Spheroids, Cellular / Q000378:metabolism / Q000473:pathology
C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion
Cancer stem cell; EML4-ALK; EMT; ERK1/2