Rxivist logo

Background: CIC is a transcriptional repressor inactivated by loss-of-function mutations in several cancer types, including gliomas, lung cancers, and gastric adenocarcinomas. CIC alterations and/or loss of CIC activity have been associated with poorer outcomes and more aggressive phenotypes across cancer types, which is consistent with the notion that CIC functions as a tumour suppressor across a wide range of contexts. Results: Using mammalian cells lacking functional CIC, we found that CIC deficiency was associated with chromosome segregation (CS) defects, resulting in chromosomal instability and aneuploidy. These CS defects were associated with transcriptional dysregulation of spindle assembly checkpoint and cell cycle regulators. We also identified novel CIC interacting proteins, including core members of the SWI/SNF complex, and showed that they cooperatively regulated the expression of genes involved in cell cycle regulation. Finally, we showed that loss of CIC and ARID1A cooperatively increased CS defects and reduced cell viability. Conclusions: Our study ascribes a novel role to CIC as an important regulator of the cell cycle and demonstrates that loss of CIC can lead to chromosomal instability and aneuploidy in human and murine cells through defects in CS, providing insight into the underlying mechanisms of CIC's increasingly apparent role as a "pan-cancer" tumour suppressor.

Download data

  • Downloaded 500 times
  • Download rankings, all-time:
    • Site-wide: 31,478 out of 89,581
    • In cancer biology: 1,006 out of 3,161
  • Year to date:
    • Site-wide: 33,186 out of 89,581
  • Since beginning of last month:
    • Site-wide: 21,733 out of 89,581

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)