Non-Redundant and Overlapping Oncogenic Readouts of Non-Canonical and Novel Colorectal Cancer KRAS and NRAS Mutants
作者： Krizelle Mae M. Alcantara , Joshua Reginald P. Malapit , Ryan Timothy D. Yu , Jose Antonio Ma. G. Garrido , John Paul T. Rigor
DOI: 10.3390/CELLS8121557
关键词: ETS transcription factor family 、 Cancer research 、 Epidermal growth factor receptor 、 Neuroblastoma RAS viral oncogene homolog 、 Oncogene 、 Signal transduction 、 KRAS 、 ELK1 、 Carcinogenesis 、 Biology
摘要: RAS oncogene family members are molecular switches of signaling pathways that control cell growth, proliferation, differentiation, and survival. In colorectal cancer, Kirsten-RAS (KRAS) neuroblastoma-RAS (NRAS) the commonly mutated isoforms. Activating mutations in result cellular transformation independent upregulated epidermal growth factor receptor (EGFR)-initiated signaling. The present study characterized functional consequences non-canonical/novel KRAS NRAS mutants identified a targeted next-generation sequencing cancer specimens from Filipino patients. vitro assays NIH3T3 cells showed similar to canonical G12D mutant, overexpression G12S, A59T, Y137C, but not A11V, confer higher proliferation migration rates. HCT116 transfected with novel A11V G12D, mutants, display enhanced resistance apoptosis. All four induce gross changes F-actin cytoskeletal organization morphology cells. Only G12S A59T appear deregulate extracellular signal-regulated kinase (ERK) its downstream target ETS transcription ELK1 (ELK1). Elucidation differential effector engagement responsible for variable phenotypic readouts is warranted. If validated by mouse studies clinical correlates, these can have wider implications choosing treatment options.
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