Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?

Xiangyuan Xu; Guangtao Zhang; Yijia Chen; Weina Xu; Yujing Liu; Guang Ji; Hanchen Xu

doi:10.3389/fonc.2023.1254439

Can proline dehydrogenase-a key enzyme involved in proline metabolism-be a novel target for cancer therapy?

Front Oncol. 2023 Nov 6:13:1254439. doi: 10.3389/fonc.2023.1254439. eCollection 2023.

Authors

Xiangyuan Xu^{1

2}, Guangtao Zhang¹, Yijia Chen³, Weina Xu⁴, Yujing Liu^{1

2}, Guang Ji^{1

2}, Hanchen Xu^{1

2}

Affiliations

¹ Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, Shanghai, China.
³ Department of Gynecology, LongHua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
⁴ Shanghai Pudong New Area Zhoujiadu Community Health Service Center, Shanghai, China.

Abstract

Emerging evidence suggests that proline metabolism is important for regulating the survival and death of different types of cancer cells. Proline dehydrogenase (PRODH), an enzyme catalyzing proline catabolism, and the degradation products of proline by PRODH, such as ATP and ROS, are known to play critical roles in cancer progression. Notably, the role of PRODH in cancer is still complicated and unclear, and primarily depends on the cancer type and tumor microenvironment. For instance, PRODH induces apoptosis and senescence through ROS signaling in different types of cancers, while as a protumor factor, PRODH promotes malignant phenotypes of certain tumors under stresses such as hypoxia. In order to assess whether PRODH can serve as a novel target for cancer therapy, we will provide an overview of the biological functions of PRODH and its double-edged role in cancer in this article.

Keywords: ProDH; cancer metabolism; cancer therapy; immunosuppression; proline metabolism.

Publication types

Review

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Nature Science Foundation of China( 82104466; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation(2021KJ03-12); Shanghai Rising-Star Program( 20QA1409300; and the Program for Young Eastern Scholar at Shanghai Institutions of Higher Learning( QD2019034; Young Elite Scientists Sponsorship Program by CACM. Health Research Project of Shanghai Pudong New Area Health Commission (PKJ2021-Y101)