Serine racemase (SRR), cancer metabolism

Cancer (colon cancer)

It is known that cancer cells have acquired metabolic dynamics that are completely different from those of normal tissues in order to give themselves an advantage in survival, and in recent years, attempts have been made to identify cancer-specific metabolic pathways and develop therapeutic approaches that target these pathways.
We have demonstrated that a metabolic enzyme called serine racemase (SRR), whose function has been revealed only in the central nervous system, is involved in the metabolic pathway that produces pyruvate from L-serine in colorectal cancer, and promotes the proliferation of colorectal cancer by contributing to histone acetylation, maintenance of mitochondrial quantity and quality, and apoptosis resistance. We also confirmed by immunohistochemical staining that the expression of SRR is increased in human colorectal adenomas and colorectal cancer tissues compared to non-tumor tissues (colorectal cancer > colorectal adenoma > non-tumor tissues). We also demonstrated that an SRR inhibitor suppressed the proliferation of colorectal cancer cells, and showed a significant proliferation-suppressing effect in combination with existing anticancer drugs, suggesting the possibility that SRR could be a therapeutic target for colorectal cancer.
Colorectal cancer is one of the most common cancers in Japan in terms of both incidence and mortality, and it is difficult to cure in cases where surgery is inoperable or recurrent. Based on the results of this study, it is expected that SRR will become a new drug target that targets the metabolism of colorectal cancer.

- Discovery of a new drug target related to cancer metabolism

- There is a possibility that this could lead to a new treatment for colorectal cancer.
・It has the effect of reducing chemotherapy resistance in colon cancer cells and enhancing the effects of chemotherapy.

・Treatment of intractable colon cancer

・Analysis of D-amino acids in the intestinal tract (feces) may lead to the establishment of risk prediction and diagnostic methods for colorectal cancer.

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1. Ohshima K, et al. Serine racemase enhances growth of colorectal cancer by producing pyruvate from serine. Nature Metabolism 2, 81–96 (2020)