Estrogen receptor α inhibits Caveolin 1 translation by promoting m6A-dependent miR199a-5p maturation to confer nab-paclitaxel resistance.

ABSTRACT: Estrogen receptor positive (ER+) breast cancer patients exhibit poorer responsiveness to nab-paclitaxel compared to ER negative (ER-) patients, with the underlying mechanisms remaining unknown. Caveolin 1 (CAV1) is a membrane invagination protein critical for the endocytosis of macromolecules including albumin-bound chemotherapeutic agents. Here, we demonstrate that ERα limits the efficacy of nab-paclitaxel in breast cancer cells while genetic or pharmacological inhibition of ERα increased the sensitivity of ER+ breast cancer cells to nab-paclitaxel. Notably, CAV1 expression inversely correlates with ERα and relates to improved clinical outcomes from nab-paclitaxel treatment. Importantly, ERα stimulates m6A dependent maturation of miR199a-5p, which is elevated in ER+ breast cancer, to inhi

SUBMITTER: Zhang J 

PROVIDER: S-EPMC10767350 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature