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CKAP2L promotes non-small cell lung cancer progression through regulation of transcription elongation


ABSTRACT: ABSTRACT Chromosomal instability (CIN) is a driver of clonal diversification and intra-tumor heterogeneity, providing genetic diversity that contributes to tumor progression. It is estimated that ?80% of solid cancers, including non-small cell lung cancer (NSCLC), exhibit features of CIN, which affect tumor growth and response to therapy. However, the molecular mechanism connecting CIN to carcinogenesis is still poorly understood. Through an RNAi screen performed on genes involved in CIN and overexpressed in human lung adenocarcinoma samples we identified the Cytoskeleton-associated protein 2-like (CKAP2L) as a potential oncogene that promotes lung cancer cell proliferation and growth in vitro and in vivo. Mechanistically, CKAP2L directly interacts with RNA Pol II and regulates transcription elongation of key genes involved in spindle assembly checkpoint, chromosome segregation, cell cycle and E2F signaling. Furthermore, CKAP2L depletion increased sensitivity of NSCLC cells to alvocidib, a pan CDK inhibitor, leading to a significant reduction of cell proliferation and increase in cell death. Altogether, these findings shed light on the molecular mechanisms through which CKAP2L, a protein involved in CIN, promotes cancer progression and suggest that simultaneous inhibition of CKAP2L and alvocidib treatment could represent a valid therapeutic option in NSCLC patients.

ORGANISM(S): Homo sapiens (human)

SUBMITTER: Michela Garofalo 

PROVIDER: S-BSST569 | biostudies-other |

REPOSITORIES: biostudies-other

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