Commentary: Cancer-testis antigen lactate dehydrogenase C4 as a novel biomarker of male infertility and cancer

We read with great interest the recently published review by Jing W et al. (1) on the relevance of the cancer testis antigen (CTA) Lactate Dehydrogenase C (LDHC) in male infertility and cancer. In their review, the authors discussed the mechanisms by which LDHC regulates sperm function and supports tumorigenesis. Overall, its best characterized function is the regulation of glycolysis whereby LDHC catalyzes the interconversion of pyruvate and NADH to lactate and NAD+ resulting in rapid ATP production. The loss of LDHC expression and concomitant reduction in ATP production greatly compromises spermatozoa motility and cAMP/PKA-mediated sperm capacitation preceding fertilization. In cancer, the enzymatic activity of LDHC plays a key role in metabolic reprogramming of cancer cells from oxidative phosphorylation to aerobic glycolysis to support the increasing energy demands for rapid growth as described by Jing W et al. However, the pro-tumorigenic effects of this metabolic switch extend beyond cancer cell energetics. We have previously reported on the role of cancer cell metabolic reprogramming in shaping an immunosuppressive environment whereby metabolic competition for glucose directly impairs immune cell functionality and lactic acidosis further inhibits the proliferation and activity of infiltrating cytotoxic immune cells (2). These findings suggest that cancer cell metabolism and immunosuppression are closely interconnected, however, it remains to be determined whether LDHC plays a role at this interface.

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Published in: Frontiers in Oncology
License: https://creativecommons.org/licenses/by/4.0/
See article on publisher's website: https://dx.doi.org/10.3389/fonc.2023.1115620