Cullin-5 deficiency orchestrates the tumor microenvironment to promote mammary tumor development through CREB1-CCL2 signaling.

ABSTRACT: Breast cancer-associated gene 1 (Brca1) deficiency induces the onset of breast cancer formation, accompanied with extensive genetic alterations. Here, we used both the sleeping beauty transposon mutagenesis system and CRISPR-Cas9-mediated genome-wide screening in mice to identify potential genetic alterations that act synergistically with Brca1 deficiency to promote tumorignesis. Both approaches identified Cullin-5 as a tumor suppressor, whose mutation enabled Brca1-deficient cell survival and accelerated tumorigenesis by orchestrating tumor microenvironment. Cullin-5 suppresses cell growth through ubiquitylating and degrading adenosine 3',5'-monophosphate-responsive element binding protein 1 (CREB1), especially under protein damage condition. Meanwhile, Cullin-5 defic

SUBMITTER: Chen S 

PROVIDER: S-EPMC9858512 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature