The PML1-WDR5 axis regulates H3K4me3 marks and promotes stemness of estrogen receptor-positive breast cancer.

ABSTRACT: The alternative splicing of PML precursor mRNA gives rise to various PML isoforms, yet their expression profile in breast cancer cells remains uncharted. We discovered that PML1 is the most abundant isoform in all breast cancer subtypes, and its expression is associated with unfavorable prognosis in estrogen receptor-positive (ER+) breast cancers. PML depletion reduces cell proliferation, invasion, and stemness, while heterologous PML1 expression augments these processes and fuels tumor growth and resistance to fulvestrant, an FDA-approved drug for ER + breast cancer, in a mouse model. Moreover, PML1, rather than the well-known tumor suppressor isoform PML4, rescues the proliferation of PML knockdown cells. ChIP-seq analysis reveals significant overlap between P

SUBMITTER: Kao HY 

PROVIDER: S-EPMC10503857 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature