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

TL;DR

This study shows that the enzyme TKT promotes kidney cancer growth by boosting glucose metabolism and working with another protein called PKM2.

Contribution

The study identifies a new functional link between TKT and PKM2 in driving metabolic changes in renal cell carcinoma.

Findings

TKT promotes glycolysis and tumor progression in renal cell carcinoma.

TKT expression is elevated in RCC tissues and linked to poor patient outcomes.

TKT and PKM2 work together to enhance cancer cell growth and invasion.

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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