EML4-ALK induces epithelial–mesenchymal transition consistent with cancer stem cell properties in H1299 non-small cell lung cancer cells

• DOI: 10.1016/j.bbrc.2015.02.114
• Publication Date: 2015-02-28T11:05:07Z
• Authors: Fuchun Guo; Xiaoke Liu; Qin Qing; Yaxiong Sang; Chengjun Feng; Xiaoyu Li; Li Jiang; Pei Su; Yongsheng Wang
• Keywords: 0301 basic medicine; Epithelial-Mesenchymal Transition; Lung Neoplasms; Oncogene Proteins, Fusion; MAP Kinase Signaling System; 3. Good health; 03 medical and health sciences; Cell Transformation, Neoplastic; Phenotype; Cell Movement; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Spheroids, Cellular; Neoplastic Stem Cells; Humans; Neoplasm Invasiveness; Oncogene Fusion

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.