Slc16a3, also named as MCT4, is a transporter encoding monocarboxylate transporter 4 within the SLC16 gene family. It mediates the proton-linked efflux of lactic acid, a metabolite of glycolysis, across the plasma membrane, playing a crucial role in energy metabolism, especially in tumor cells [4]. It is involved in multiple biological pathways, and its study via genetic models can help elucidate its functions.

In cancer research, genetic and pharmacological inhibition of Slc16a3 in tumor cells has shown promising results. Inhibiting Slc16a3 reduces glycolytic activity and lactic acid production, ameliorates the immunosuppressive tumor microenvironment, and boosts antitumor effects via anti-PD-1 blockade, suggesting it may reverse tumor resistance to immunotherapy [1]. In hepatocellular carcinoma, knockdown of Slc16a3 decreases extracellular lactate concentration, alleviates hypoxia, and induces ferroptosis, indicating it could be a potential therapeutic target for HCC [2]. In bladder cancer, high expression of Slc16a3 is related to poor prognosis, and it may influence immune infiltration by regulating metabolism and m6A methylation [3].

In conclusion, Slc16a3 is essential for lactic acid transport and energy metabolism. Studies using gene-knockout or knockdown models have revealed its significant roles in various cancer-related processes. These findings suggest that targeting Slc16a3 could be a novel approach for cancer therapy, highlighting its potential as a therapeutic target in multiple cancer types.

References:

1. Yu, Ting, Liu, Zhaoyun, Tao, Qingxu, Wu, Meng, Yu, Jinming. 2024. Targeting tumor-intrinsic SLC16A3 to enhance anti-PD-1 efficacy via tumor immune microenvironment reprogramming. In Cancer letters, 589, 216824. doi:10.1016/j.canlet.2024.216824. https://pubmed.ncbi.nlm.nih.gov/38522774/

2. Shen, Jie, Wu, Zhongkai, Zhou, Yu, Zhao, Kailiang, Ding, Youming. 2024. Knockdown of SLC16A3 decreases extracellular lactate concentration in hepatocellular carcinoma, alleviates hypoxia and induces ferroptosis. In Biochemical and biophysical research communications, 733, 150709. doi:10.1016/j.bbrc.2024.150709. https://pubmed.ncbi.nlm.nih.gov/39303526/

3. Li, Chengjun, Chu, Guangdi, Ma, Guofeng, Ma, Xiaocheng, Niu, Haitao. 2024. SLC16A3 is a Prognostic Marker and Affects Immune Regulation in Bladder Cancer. In Combinatorial chemistry & high throughput screening, , . doi:10.2174/0113862073278304240614064748. https://pubmed.ncbi.nlm.nih.gov/38956920/

4. Halestrap, Andrew P. . The SLC16 gene family - structure, role and regulation in health and disease. In Molecular aspects of medicine, 34, 337-49. doi:10.1016/j.mam.2012.05.003. https://pubmed.ncbi.nlm.nih.gov/23506875/