MAP3K1/MAP2K4 mutations drive breast cancer progression by compensating for TP53 loss through inactivation of the JNK2-p53-FOSL1 axis.

ABSTRACT:

Background

Cancer progression is driven by somatic mutations, with alterations in driver genes such as tumor suppressors and oncogenes playing critical roles. In breast cancer (BRCA), mutations in MAP3K1 and MAP2K4 are recurrent, especially in estrogen receptor-positive (ER⁺) subtypes, yet their functional significance and mechanistic contributions remain incompletely understood. This study aims to elucidate the role of MAP3K1/MAP2K4 mutations in BRCA pathogenesis.

Methods

We performed integrated genomic analyses using data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohorts. Functional validation was conducted in breast cancer cell lines (e.g., MCF-7, ZR-75-1) using shRNA-mediated knockdown, over

SUBMITTER: Hu S 

PROVIDER: S-EPMC12821902 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature