Developments in the study of the role of lactate metabolism in the genesis and progression of thyroid cancer

Lei Shi^1,2,3Xuyang Zhong^4,5Jiafeng Liu³Yong Ying¹Zibing Liao⁶Jin Liu⁶LIwen Zhao⁶Xiangtai Zeng^1*Jianing Zhong^6,7*

• ¹Department of Thyroid and Hernia Surgery, First Affiliated Hospital of Gannan Medical University, Ganzhou, China
• ²Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, China
• ³Ganzhou Key Laboratory of Thyroid Cancer, First Affiliated Hospital of Gannan Medical University, GANZHOU, China
• ⁴Gannan Medical University, Ganzhou, China
• ⁵Department of Clinical Medicine, First Clinical College, Gannan Medical University, GANZHOU, China
• ⁶Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, GANZHOU, China
• ⁷Basic Clinical College,Gannan Medical University, GANZHOU, China

Thyroid carcinoma is among the most common endocrine system malignancies. Lactate metabolism and lactylation modification roles in carcinogenesis and development have garnered more interest in recent years. The expression and function of lactate transporters (MCTs) and significant metabolic enzymes are included in our summary of the characterisation of lactate metabolism in thyroid cancer. We systematically dissect the multifaceted regulatory circuits governing lactate metabolism by integrating three pivotal dimensions: (i) canonical signaling cascades; (ii) tumor-microenvironmental variables, most notably hypoxia and acidosis; and (iii) the emerging epigenetic paradigm of lactylation, which dynamically reprograms the catalytic efficiency of rate-limiting enzymes and reshapes the transcriptional landscape of metabolic genes, thereby precisely coordinating lactate homeostasis. Furthermore, this review explains how lactate promotes thyroid cancer cell growth, invasion, metastasis, angiogenesis, and immunosuppression. It also discusses how lactate may contribute to treatment resistance. This paper provides new ideas for future research and clinical translation by summarizing the key findings and clinical significance of the current research on lactate metabolism in thyroid cancer, anticipating future research directions, and applying the development of more effective treatments that target lactate metabolism to clinical practice.