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Yanshu, L and Rakesh , Kumar (2018) A mandatory role of nuclear PAK4-LIFR axis in breast-to-bone metastasis of ERα-positive breast cancer cells. Oncogene. ISSN 1476-5594

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Abstract

The mechanism of estrogen receptor alpha (ERα)-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 ERα-mediated transactivation in a 17β-estradiol (E2)-dependent manner and promotes PAK4–ERα axis-mediated bone metastasis by targeting leukemia inhibitory factor receptor (LIFR) in ERα-positive breast cancer. An evaluation of clinical breast cancer samples revealed that nPAK4 is linked to ERα expression and appears to be associated with a poor prognosis in bone metastatic breast cancer. PAK4 bound and co-translocated with ERα from the cytoplasm to the nucleus upon stimulation with E2. nPAK4 enhanced the invasive potential of ERα-positive breast cancer cells in vitro and promoted breast cancer metastasis in vivo. Mechanistically, nPAK4 promoted the metastasis of ERα-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 ERα-positive breast cancer bone metastasis.

Item Type: Article
Subjects: Cancer Research
Depositing User: Rgcb Library
Date Deposited: 03 Oct 2018 10:16
Last Modified: 03 Oct 2018 10:17
URI: http://rgcb.sciencecentral.in/id/eprint/693

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