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

被引：11

作者：

Thapa, Dinesh ^{[1
,8
]}

Huang, Shih-Bo ^{[1
]}

Munoz, Amanda R. ^{[1
]}

Yang, Xiaoyu ^{[1
]}

Bedolla, Roble G. ^{[1
]}

Hung, Chia-Nung ^{[2
]}

Chen, Chun-Liang ^{[2
]}

Huang, Tim H. -M. ^{[2
,3
]}

Liss, Michael A. ^{[1
,3
]}

Reddick, Robert L. ^{[4
]}

Miyamoto, Hiroshi ^{[5
]}

Kumar, Addanki P. ^{[1
,2
,3
,6
,7
]}

Ghosh, Rita ^{[1
,2
,3
,6
]}

机构：

[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Urol, Sch Med, San Antonio, TX 78229 USA

[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, Sch Med, San Antonio, TX 78229 USA

[3] Univ Texas Hlth Sci Ctr San Antonio, Mays Canc Ctr, Sch Med, San Antonio, TX 78229 USA

[4] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, Sch Med, San Antonio, TX 78229 USA

[5] Univ Rochester, Med Ctr, Dept Pathol & Lab Med, Rochester, NY 14642 USA

[6] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, Sch Med, San Antonio, TX 78229 USA

[7] South Texas Vet Hlth Care Syst, San Antonio, TX USA

[8] Dana Farber Canc Inst, Dept Med Oncol, 450 Brookline Ave, Boston, MA 02115 USA

来源：

COMMUNICATIONS BIOLOGY | 2020年 / 3卷 / 01期

关键词：

OXIDATIVE STRESS; MESENCHYMAL TRANSITION; LIVER FIBROSIS; NQO1; EXPRESSION; METASTASIS; PROGRESSION; MECHANISMS; RESISTANCE; ROLES;

D O I：

10.1038/s42003-019-0720-z

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 TGF beta signaling and mesenchymal markers. TGF beta 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 TGF beta signaling molecules may serve as a better signature to predict biochemical recurrence. Thapa et al find that depletion of the antioxidant enzyme NAD[P]H:Quinone Oxidoreductase 1 (NQO1) accelerates prostate tumorigenesis and induces the epithelial-to-mesenchymal transition by activating TGF beta signaling. They also find that low NQO1 is associated with mesenchymal signature and biochemical recurrence in clinical samples.

引用

页数：12

共 51 条

[1] NQ01 stabilizes p53 through a distinct pathway [J].