Lactate inhibits interferon-α response in ovarian cancer by inducing STAT1 ubiquitin degradation

Xinhuai Dong & Jie Yao et al. · 2023-10-31

7Citations
The emergence of lactate, produced by lactate dehydrogenase A (LDHA), as an important regulator of the immune response in tumor development has garnered attention in recent research. But, many questions still need to be clarified regarding the relationship between lactate and anti-tumor immunity. Here, we reported that both exogenous and endogenous lactate reduced the protein level and activation of the signal transducer and activator of transcription 1(STAT1) in ovarian cancer cells. As a consequence, the expression of IFNα-STAT1 regulated genes was weakened. This, in turn, weakened the antitumor effect of IFNα by impeding NKT and CD8
Links
DOIPubMed
Journal
International Immunopharmacology
TL;DR

Lactate is revealed as a negative regulator of the IFNα-STAT1 signaling axis in ovarian cancer, suggesting that strategies aimed at targeting lactate for ovarian cancer prevention and treatment should consider the impact on the IFNα-STAT1 response.

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Authors
Xinhuai Dong, Can Lin, Xu Lin, Chong Zeng, Liming Zeng, Zibo Wei, Xiaokang Zeng, Jie Yao
Funding
Natural Science Foundation of Guangdong Province Grant 2021A1515010928Medical Science and Technology Foundation of Guangdong Province Grant B2022177Southern Medical University Grant SRSP2019009Southern Medical University Grant SRSP2021002Southern Medical University Grant SRSP2021006Southern Medical University Grant SRSP2021012Southern Medical University Grant YNZX0002Southern Medical University Grant YNZX0003Department of Education of Guangdong Province Grant 2020KTSCX024Basic and Applied Basic Research Foundation of Guangdong Province Grant 2022A1515220197