HDAC inhibitors stimulate LIFR when it is repressed by hypoxia or PTHrP in breast cancer.

ABSTRACT: Breast cancer cells frequently disseminate to the bone marrow, where they either induce osteolysis or enter a dormant state. Downregulation of leukemia inhibitory factor receptor (LIFR), a known breast tumor suppressor, enables otherwise dormant MCF7 human breast cancer cells to become aggressively osteolytic. Hypoxia (low oxygen tensions), which may develop in tumors as a pathological response to the metabolic demands of the proliferating cells and as a physiological state in the bone, downregulates LIFR in breast cancer cells independent of hypoxia-inducible factor (HIF) signaling. However, the mechanism by which LIFR is repressed in hypoxia is unknown. Histone deacetylase (HDAC) inhibitors stimulate LIFR by increasing histone acetylation in the proximal promoter and induce a dormancy ph

SUBMITTER: Edwards CM 

PROVIDER: S-EPMC8661052 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature