Loss of USP28 and SPINT2 expression promotes cancer cell survival after whole genome doubling.

ABSTRACT:

Background

Whole genome doubling is a frequent event during cancer evolution and shapes the cancer genome due to the occurrence of chromosomal instability. Yet, erroneously arising human tetraploid cells usually do not proliferate due to p53 activation that leads to CDKN1A expression, cell cycle arrest, senescence and/or apoptosis.

Methods

To uncover the barriers that block the proliferation of tetraploids, we performed a RNAi mediated genome-wide screen in a human colorectal cancer cell line (HCT116).

Results

We identified 140 genes whose depletion improved the survival of tetraploid cells and characterized in depth two of them: SPINT2 and USP28. We found that SPINT2 is a general regulator of CDKN1A transcription via histone acetylation. Using mass spectrometry and i

SUBMITTER: Bernhard SV 

PROVIDER: S-EPMC8881269 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature