Microtubule Association of EML4-ALK V3 Is Key for the Elongated Cell Morphology and Enhanced Migration Observed in V3 Cells.

ABSTRACT: The EML4-ALK oncogene drives tumour progression in approximately 5% of cases of non-small-cell lung cancers. At least 15 EML4-ALK variants have been identified, which elicit differential responses to conventional ALK inhibitors. Unfortunately, most, if not all, patients eventually acquire resistance to these inhibitors and succumb to the disease, which warrants the need for alternative targets to be identified. The most aggressive variant, EML4-ALK variant 3 (V3), assembles into a complex on interphase microtubules together with the NEK9 and NEK7 kinases, which leads to the downstream phosphorylation of NEK7 substrates. Overall, this promotes an elongated cell morphology and an enhanced migratory phenotype, which likely contributes to the increased metastasis often seen in V3 patients. Her

SUBMITTER: Papageorgiou S 

PROVIDER: S-EPMC11639804 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature