Reduced expression of FRG1 facilitates breast cancer progression via GM-CSF/MEK-ERK axis by abating FRG1 mediated transcriptional repression of GM-CSF.

ABSTRACT: Multiple molecular subtypes and distinct clinical outcomes in breast cancer, necessitate specific therapy. Moreover, despite the improvements in breast cancer therapy, it remains the fifth cause of cancer-related deaths, indicating the involvement of unknown genes. To identify novel contributors and molecular subtype independent therapeutic options, we report reduced expression of FRG1 in breast cancer patients, which regulates GM-CSF expression via direct binding to its promoter. Reduction in FRG1 expression enhanced EMT and increased cell proliferation, migration, and invasion, in breast cancer cell lines. Loss of FRG1 increased GM-CSF levels which activated MEK/ERK axis and prevented apoptosis by inhibiting p53 in an ERK-dependent manner. FRG1 depletion in the mouse model increased tumo

SUBMITTER: Mukherjee B 

PROVIDER: S-EPMC9633810 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature