Work

Attenuation of NAD[P]H:quinone oxidoreductase 1 aggravates prostate cancer and tumor cell plasticity through enhanced TGFβ signaling

Year: 2020

Type: article

Abstract: NAD[P]H:quinone oxidoreductase 1 (NQO1) regulates cell fate decisions in response to stress. Oxidative stress supports cancer maintenance and progression. Previously we showed that knockdown of NQO1 (NQO1 low ) prostate cancer cells upregulate pro-inflammatory cytokines and survival under hormone-deprived conditions. Here, we tested the ability of NQO1 low cells to form tumors. We found NQO1 low cells form aggressive tumors compared with NQO1 high cells. Biopsy specimens and circulating tumor cells showed biochemical recurrent prostate cancer was associated with low NQO1. NQO1 silencing was sufficient to induce SMAD-mediated TGFβ signaling and mesenchymal markers. TGFβ treatment decreased NQO1 levels and induced molecular changes similar to NQO1 knockdown cells. Functionally, NQO1 depletion increased migration and sensitivity to oxidative stress. Collectively, this work reveals a possible new gatekeeper role for NQO1 in counteracting cellular plasticity in prostate cancer cells. Further, combining NQO1 with TGFβ signaling molecules may serve as a better signature to predict biochemical recurrence.

Source: Communications Biology

DOI: 10.1038/s42003-019-0720-z

Authors: Dinesh Thapa, Shih-Bo Huang, Amanda R. Muñoz, Xiaoyu Yang, Roble G. Bedolla, Chia-Nung Hung, Chun-Liang Chen, Tim H.-M. Huang, Michael A. Liss, Robert L. Reddick, Hiroshi Miyamoto, Addanki P. Kumar, Rita Ghosh

Institutions: The University of Texas at San Antonio Health Science Center, Dana-Farber Cancer Institute, Mays Cancer Center at UT Health San Antonio, University of Rochester Medicine, University of Rochester, South Texas Veterans Health Care System

Language: English

Topic: Prostate Cancer Treatment and Research

Subfield: Pulmonary and Respiratory Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,290

Funders: U.S. Department of Health and Human Services, Cancer Prevention and Research Institute of Texas, National Institutes of Health, University of Texas Health Science Center at San Antonio, National Cancer Institute, National Institute of General Medical Sciences, National Center for Complementary and Integrative Health

Awards: Systems Analysis of Epigenomic Architecture in Cancer Progression, San Antonio Biomedical Education and Research, Oxidative stress in prostate cancer: Efficacy of antioxidants in Nkx3.1; Pten mod, G3446954139, The Single-Cell Biopsy and Characterization Core (SBCC) at The University of Texas Health Science at San Antonio, Interrogating Epigenetic Changes in Cancer Genomes, G6078305876, Oxidative stress and programmed death pathways: Cross talk in pancreatic cancer, UTHSCSA Cancer Research Training Program, G7226629610, G8006546248

OpenAlex ID: W2997190882

FWCI: 1.832

Cites: 52

Cited by: 19

Related to: 10