A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ER?-positive breast cancer cells.

ABSTRACT: The mechanism of estrogen receptor alpha (ER?)-positive breast cancer-associated bone metastasis is poorly understood. In this article, we report that nuclear p21-activated kinase 4 (nPAK4) is a novel repressor of ER?-mediated transactivation in a 17?-estradiol (E2)-dependent manner and promotes PAK4-ER? axis-mediated bone metastasis by targeting leukemia inhibitory factor receptor (LIFR) in ER?-positive breast cancer. An evaluation of clinical breast cancer samples revealed that nPAK4 is linked to ER? expression and appears to be associated with a poor prognosis in bone metastatic breast cancer. PAK4 bound and co-translocated with ER? from the cytoplasm to the nucleus upon stimulation with E2. nPAK4 enhanced the invasive potential of ER?-positive breast cancer cells in vitro and promoted breast cancer metastasis in vivo. Mechanistically, nPAK4 promoted the metastasis of ER?-positive?breast cancer cells by targeting LIFR, a bone metastasis suppressor. Strikingly, the nuclear accumulation of PAK4 might promote aggressive phenotypes, highlighting nPAK4 as a novel predictive biomarker for ER?-positive breast cancer bone metastasis.

SUBMITTER: Li Y 

PROVIDER: S-EPMC6367215 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature