EML4-ALK induces cellular senescence in mortal normal human cells and promotes anchorage-independent growth in hTERT-transduced normal human cells

Abstract Background Chromosomal inversions involving anaplastic lymphoma kinase ( ALK ) and echinoderm microtubule associated protein like 4 EML4 generate a fusion EML4-ALK in non-small cell lung cancer (NSCLC). The understanding of function can be improved by functional study using normal human cells. Methods Here we for the first time conduct such to examine effects on proliferation, cellular senescence, DNA damage, gene expression profiles transformed phenotypes. Results lentiviral mortal, fibroblasts caused, through its constitutive activity, an early induction senescence with accumulated upregulation p16 INK4A p21 WAF1 , senescence-associated β-galactosidase (SA-β-gal) activity. In contrast, when was expressed transduced telomerase reverse transcriptase (hTERT), which is activated vast majority NSCLC, cells showed accelerated proliferation acquired anchorage-independent growth ability soft-agar medium, without chromosome aberration, nor p53 mutation. induced phosphorylation STAT3 both mortal hTERT-transduced cells, but RNA sequencing analysis suggested that different signaling pathways contributed phenotypic outcomes these While also hTERT-immortalized bronchial epithelial vitro, alone did not cause detectable vivo tumorigenicity immunodeficient mice. Conclusions Our data indicate hTERT critical manifest vitro transforming activity This provides isogenic pairs expression.