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  3. Cysteine dioxygenase 1 attenuates the proliferation via inducing oxidative stress and integrated stress response in gastric cancer cells

Cysteine dioxygenase 1 attenuates the proliferation via inducing oxidative stress and integrated stress response in gastric cancer cells

  • Cell Death Discov. 2022 Dec 16;8(1):493. doi: 10.1038/s41420-022-01277-x.
Gang Ma # 1 2,  Zhenzhen Zhao # 1 2,  Yang Qu 2 3,  Fenglin Cai 1 2,  Siya Liu 1 2,  Han Liang 1 2,  Rupeng Zhang 1 2,  Jingyu Deng 4 5
Affiliations

Affiliations

  • 1 Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P. R. China.
  • 2 Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China.
  • 3 Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P. R. China.
  • 4 Department of Gastric Surgery, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, P. R. China. dengery@126.com.
  • 5 Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China. dengery@126.com.
  • # Contributed equally.
PMID: 36526626 DOI: 10.1038/s41420-022-01277-x
Abstract

Whereas cysteine dioxygenase 1 (CDO1) expression is lost due to its hypermethylated promoter across a range of Cancer types including gastric Cancer (GC), its functions and molecular underpinnings remain largely unknown. Here we demonstrate that reduced CDO1 expression is indicative of unfavorable prognosis in patients with GC. CDO1 overexpression in GC cells markedly inhibits cellular proliferation in vitro and in vivo. Mechanistically, CDO1 exerts this cytostatic effect via increasing oxidative stress and thus activating integrated stress response (ISR) in GC cells. High throughput screening (HTS) of antioxidants library identifies that Engeletin, a flavanonol glycoside, blunts oxidative stress and the ISR to relieve the inhibitory effect of CDO1 on the proliferation in GC cells. Additionally, genetic disruption or pharmaceutical inhibition of the ISR boosts the growth in the GC cells with CDO1 expression. Our data uncover the molecular mechanisms underlying the cytostatic function of CDO1 in the proliferation of GC cells.

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