A tumor-associated splice-isoform of <i>MAP2K7</i> drives dedifferentiation in MBNL1-low cancers via JNK activation
Debleena Ray, Yu Chye Yun, Muhammad Idris, Shanshan Cheng, Arnoud Boot, Tan Bee Huat Iain, Steve Rozen, Patrick Tan, David Epstein
Abstract
Significance Targeting stem-like cells in cancer is critical to overcoming resistance and relapse post chemotherapy or immunotherapy. We elucidate an alternative-splicing driven mechanism of cancer dedifferentiation and define a molecular context wherein stem-like tumor cells show enhanced susceptibility to JNK inhibition. MBNL1 and MAP2K7 ∆exon2 can prognosticate patients for JNK inhibition that can render stem-like tumor cells susceptible to therapy.
Topics & Concepts
Cancer researchContext (archaeology)Stem cellRNA splicingAlternative splicingGene isoformCancer stem cellImmunotherapyMedicineCancerBiologyChemistryCell biologyInternal medicineGeneGeneticsPaleontologyRNARNA Research and SplicingRNA modifications and cancerinterferon and immune responses