Accumulating results of clinical trials lead targeted therapies to be the first choice for unresectable or recurrent lung cancer with driver mutations. Echinoderm Microtubule Associated Protein Like 4 (EML4) - Anaplastic lymphoma kinase (ALK) fusion is known as such a driver mutation. It presents in 3-6% of non-small cell lung carcinoma (NSCLC). EML4-ALK fusion protein generate the constitutive ALK kinase activity in NSCLC. The basic understanding of EML4-ALK remains insufficient due to the lack of functional studies using normal human cells. We investigated the role of EML4-ALK in mortal and immortalized normal human cells. The expression of EML4-ALK in normal, mortal human fibroblasts caused accumulated DNA damage, telomere shortening and the early induction of cellular senescence with senescence-associated beta-galactosidase activity and upregulation of p16INK4A and p21WAF1. In contrast, when EML4-ALK was expressed in telomerase reverse transcriptase (hTERT)-immortalized normal huma..... READ ARTICLE
Cancer Research DOI:10.1158/1538-7445.AM2020-4900
Authors: Masaru Matsumoto, Akihiko Miyanaga, Jessica Beck, Izumi Horikawa, Mohammed Khan, Delphine Lissa, Masahiro Seike, Akihiko Gemma, Hiroyuki Mano and Curtis Harris
