2. Academic Validation
  3. TKT drives renal cell carcinoma progression through metabolic reprogramming and synergistic interaction with PKM2

TKT drives renal cell carcinoma progression through metabolic reprogramming and synergistic interaction with PKM2

  • Cell Death Discov. 2025 Nov 18;11(1):537. doi: 10.1038/s41420-025-02837-7.
Qianqing Wang # 1,  Anqun Tang # 2,  Qingxin Zhuang # 3,  Haifeng Xu # 4,  Shiping Xu 2,  Jing Zhang 2,  Yao Wang 2,  Liantao Li 2,  Sufang Chu 2,  Yan Wang 5,  Jin Bai 6 7 8,  Minle Li 9 10,  Rui Zhang 11
Affiliations

Affiliations

  • 1 Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, 453000, Henan, China.
  • 2 Cancer Institute, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China.
  • 3 Department of Oncology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, 750011, Ningxia, China.
  • 4 Department of Thoracic Surgery, Xuzhou Medical University Affiliated Hospital Sihong Branch, The First People's Hospital of Sihong County, Suqian, 223800, Jiangsu, China.
  • 5 Department of Pharmacy, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China. [email protected].
  • 6 Xinxiang Central Hospital, The Fourth Clinical College of Xinxiang Medical University, Xinxiang, 453000, Henan, China. [email protected].
  • 7 Cancer Institute, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. [email protected].
  • 8 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. [email protected].
  • 9 Cancer Institute, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. [email protected].
  • 10 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China. [email protected].
  • 11 Department of Respiratory and Critical Care Medicine, Foshan Fosun Chancheng Hospital, Foshan, 528031, Guangdong, China. [email protected].
  • # Contributed equally.
PMID: 41253799 DOI: 10.1038/s41420-025-02837-7
Abstract

Renal cell carcinoma (RCC) undergoes profound metabolic reprogramming to fuel its aggressive progression and metastatic dissemination. While Transketolase (TKT), a central metabolic enzyme, has been shown to exert dichotomous roles as either oncogenic or tumor-suppressive factors across different malignancies, its functional significance in RCC pathogenesis remains inadequately defined. In this study, we demonstrate that TKT promotes glucose metabolism in RCC by enhancing glycolysis, thereby supporting tumor progression. TKT expression is significantly elevated in RCC tissues and correlates with poor patient prognosis. Mechanistically, we uncovered a novel functional axis between TKT and the glycolytic gatekeeper Pyruvate Kinase M2 (PKM2), where their coordinated action drives metastatic progression and metabolic adaptation in RCC. Knockdown of PKM2 significantly impaired the TKT-mediated increases in glycolysis, cell proliferation, and invasive potential. Taken together, our findings highlight TKT as a pivotal regulator of metabolic reprogramming in RCC and suggest its potential as a therapeutic target for the treatment of this malignancy.

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