2. Academic Validation
  3. DHRS2 inhibits cell growth and metastasis in ovarian cancer by downregulation of CHKα to disrupt choline metabolism

DHRS2 inhibits cell growth and metastasis in ovarian cancer by downregulation of CHKα to disrupt choline metabolism

  • Cell Death Dis. 2022 Oct 3;13(10):845. doi: 10.1038/s41419-022-05291-w.
Zhenzhen Li  # 1 2,  Yue Tan  # 3,  Xiang Li 4,  Jing Quan 1 2,  Ann M Bode 5,  Ya Cao 1 2 6,  Xiangjian Luo 7 8 9 10 11 12
Affiliations

Affiliations

  • 1 Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China.
  • 2 Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, PR China.
  • 3 Hengyang Medical College, University of South China, Hengyang, 421001, Hunan, PR China.
  • 4 Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China.
  • 5 The Hormel Institute, University of Minnesota, Austin, MN, 55912, USA.
  • 6 Molecular Imaging Research Center of Central South University, Changsha, Hunan, 410078, China.
  • 7 Key Laboratory of Carcinogenesis and Invasion, Chinese Ministry of Education, Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, 410078, PR China. [email protected].
  • 8 Cancer Research Institute, School of Basic Medicine, Central South University, Changsha, Hunan, 410078, PR China. [email protected].
  • 9 Molecular Imaging Research Center of Central South University, Changsha, Hunan, 410078, China. [email protected].
  • 10 Hunan Key Laboratory of Oncotarget Gene, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, 410078, China. [email protected].
  • 11 Key Laboratory of Biological Nanotechnology of National Health Commission, Central South University, Changsha, Hunan, 410078, China. [email protected].
  • 12 National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410078, China. [email protected].
  • # Contributed equally.
PMID: 36192391 DOI: 10.1038/s41419-022-05291-w
Abstract

The short-chain dehydrogenase/reductase (SDR) superfamily has essential roles in lipid metabolism and redox sensing. In recent years, accumulating evidence highlights the emerging association between SDR family enzymes and Cancer. Dehydrogenase/reductase member 2(DHRS2) belongs to the NADH/NADPH-dependent SDR family, and extensively participates in the regulation of the proliferation, migration, and chemoresistance of Cancer cells. However, the underlying mechanism has not been well defined. In the present study, we have demonstrated that DHRS2 inhibits the growth and metastasis of ovarian Cancer (OC) cells in vitro and in vivo. Mechanistically, the combination of transcriptome and metabolome reveals an interruption of choline metabolism by DHRS2. DHRS2 post-transcriptionally downregulates choline kinase α (CHKα) to inhibit Akt signaling activation and reduce phosphorylcholine (PC)/glycerophosphorylcholine (GPC) ratio, impeding choline metabolism reprogramming in OC. These actions mainly account for the tumor-suppressive role of DHRS2 in OC. Overall, our findings establish the mechanistic connection among metabolic enzymes, metabolites, and the malignant phenotype of Cancer cells. This could result in further development of novel pharmacological tools against OC by the induction of DHRS2 to disrupt the choline metabolic pathway.

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