<i>SRP19</i> and the protein secretion machinery is a targetable vulnerability in cancers with <i>APC</i> loss.

ABSTRACT: Loss of the tumor suppressor gene (TSG) Adenomatous Polyposis Coli (APC) is a hallmark event in colorectal cancers. Since it is not possible to directly target a TSG, no treatment options are available for these patients. Here, we identify SRP19 and the protein secretion machinery as a unique vulnerability in cancers with heterozygous APC loss. SRP19 is located 15 kb from APC and is almost always codeleted in these tumors. Heterozygous APC/SRP19 loss leads to lower levels of SRP19 mRNA and protein. Consequently, cells with APC/SRP19 loss are vulnerable to partial suppression of SRP19. Moreover, we show that SRP19 is rate limiting for the formation of the Signal Recognition Particle, a complex that mediates ER-protein tra

SUBMITTER: Xi X 

PROVIDER: S-EPMC12012561 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature