Korte synopsis
Chromosomal instability (CIN) is a hallmark of cancer cells. However, CIN also decreases the fitness of non-cancer cells. To understand how non-transformed cells adapt to chromosomal instability, we performed a genome-wide CRISPR screen in murine non-cancer cells to find genes whose loss would desensitize cells to chromosomal instability. We found that loss of CDC20 helps cells to tolerate CIN and, in collaboration with the lab of Uri Ben-David, that cancer cells that express high levels of CDC20 typically display chromosomal instability. Mechanistically, decreased CDC20 levels increase the time cells spend in mitosis, providing them extra time to repair chromosome segregation defects, thus reducing CIN rates. Our work identifies CDC20 expression as a potential biomarker of CIN and increased sensitivity to drugs that induce CIN.
Zheng S*, Raz L*, Zhou L*, Cohen-Sharir Y, Tian R, Ippolito MR, Gianotti S, Saad R, Wardenaar R, Broekhuis M, Suarez Peredo Rodriguez M, Wobben S, van den Brink A, Bakker P, Santaguida S, Foijer F#, Ben-David U#.
High CDC20 levels increase sensitivity of cancer cells to MPS1 inhibitors. EMBO Rep. 2025 Jan 21.
