TBK1 Regulates Prostate Cancer Dormancy Through MTOR Inhibition

Overview

Journal Neoplasia

Publisher Elsevier

Specialty Oncology

Date 2013 Sep 13

PMID 24027431

Citations 65

Authors

Jin Koo Kim

Younghun Jung

Jingcheng Wang

Jeena Joseph

Anjali Mishra

Elliott E Hill

Paul H Krebsbach

Kenneth J Pienta

Yusuke Shiozawa

Russell S Taichman

Affiliations

Soon will be listed here.

Abstract

The mechanisms that regulate hematopoietic stem cell (HSC) dormancy and self-renewal are well established and are largely dependent on signals emanating from the HSC niche. Recently, we found that prostate cancer (PCa) cells target the HSC niche in mouse bone marrow (BM) during metastasis. Little is known, however, as to how the HSC niche may regulate dormancy in cancer cells. In this study, we investigated the effects of TANK binding kinase 1 (TBK1) on PCa dormancy in the BM niche. We found that binding with niche osteoblasts induces the expression of TBK1 in PCa cells PC3 and C4-2B. Interestingly, TBK1 interacts with mammalian target of rapamycin (mTOR) and inhibits its function. Rapamycin, an mTOR inhibitor, induces cell cycle arrest of PCa cells and enhances chemotherapeutic resistance of PCa cells. As a result, the knockdown of TBK1 decreases PCa stem-like cells and drug resistance in vitro and in vivo. Taken together, these results strongly indicate that TBK1 plays an important role in the dormancy and drug resistance of PCa.

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