Cancer-specific overmethylation of histone H3 lysines is necessary for methionine addiction and malignancy

Yamamoto, J.; Inubushi, S.; Han, Q.; Tashiro, Y.; Sun, Y.; Sugisawa, N.; Hamada, K.; Nishino, H.; Aoki, Y.; Miyake, K.; Matsuyama, R.; Bouvet, M.; Endo, I.; Hoffman, R. M.

doi:10.1101/2020.12.04.412437

bioRxiv · 10.1101/2020.12.04.412437

Cancer-specific overmethylation of histone H3 lysines is necessary for methionine addiction and malignancy

Yamamoto, J.·Inubushi, S.·Han, Q.·Tashiro, Y.·Sun, Y.·Sugisawa, N.·Hamada, K.·Nishino, H.·Aoki, Y.·Miyake, K.·Matsuyama, R.·Bouvet, M.·Endo, I.·Hoffman, R. M.

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Abstract

Methionine addiction is a fundamental and general hallmark of cancer and is an area of current intense interest. Methionine addiction results from the overuse of methionine by cancer cells for excess transmethylation reactions. In order to identify excess transmethylation reactions in cancer and further understand the basis of methionine addiction, we compared the histone H3 lysine-methylation status and malignancy between methionine-addicted cancer cells and their methionine-independent revertants which have regained the ability to grow on low levels of methionine or independently of exogenous methionine. The levels of trimethylated histone H3 lysine marks were reduced in methionine-independent revertants compared to parental cancer cells in vitro. Tumorigenicity and experimental metastatic potential in nude mice were also highly reduced in the methionine-independent revertants compared to the parental cells. Our present results demonstrate that overmethylation of histone H3 lysines is linked with methionine addiction of cancer and to malignancy which suggests a possible causal relationship.

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Yamamoto, J., Inubushi, S., Han, Q., Tashiro, Y., Sun, Y., Sugisawa, N., Hamada, K., Nishino, H., Aoki, Y., Miyake, K., Matsuyama, R., Bouvet, M., Endo, I., Hoffman, R. M.. 2020-12-06. Cancer-specific overmethylation of histone H3 lysines is necessary for methionine addiction and malignancy. https://doi.org/10.1101/2020.12.04.412437

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