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Co-amplification of CBX3 with EGFR or RAC1 in human cancers corroborated by a conserved genetic interaction among the genes
- Source :
- Cell Death Discovery, Vol 9, Iss 1, Pp 1-16 (2023)
- Publication Year :
- 2023
- Publisher :
- Nature Publishing Group, 2023.
-
Abstract
- Abstract Chromobox Protein 3 (CBX3) overexpression is a common event occurring in cancer, promotes cancer cell proliferation and represents a poor prognosis marker in a plethora of human cancers. Here we describe that a wide spectrum of human cancers harbors a co-amplification of CBX3 gene with either EGFR or RAC1, which yields a statistically significant increase of both mRNA and protein levels of CBX3, EGFR and RAC1. We also reveal that the simultaneous overexpression of CBX3, RAC1 and EGFR gene products correlates with a worse prognosis compared to the condition when CBX3, RAC1 and EGFR are singularly upregulated. Furthermore, we also show that a co-occurrence of low-grade amplification, in addition to high-grade amplification, between CBX3 and EGFR or RAC1 is associated with a reduced patient lifespan. Finally, we find that CBX3 and RAC1/EGFR genetically interact in the model organism Drosophila melanogaster, suggesting that the simultaneous overexpression as well as well the co-occurrence of high- or low-grade copy number alterations in these genes is not accidental and could reflect evolutionarily conserved functional relationships.
Details
- Language :
- English
- ISSN :
- 20587716
- Volume :
- 9
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Cell Death Discovery
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.5c1bd4d044584fe6b46d78e8db816a9a
- Document Type :
- article
- Full Text :
- https://doi.org/10.1038/s41420-023-01598-5