RT Journal Article
SR Electronic
T1 The linkage of methionine addiction, overmethylation of histone H3 lysines and malignancy demonstrated when cancer cells revert to methionine-independence
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.12.04.412437
DO 10.1101/2020.12.04.412437
A1 Jun Yamamoto
A1 Sachiko Inubushi
A1 Qinghong Han
A1 Yoshihiko Tashiro
A1 Norihiko Sugisawa
A1 Kazuyuki Hamada
A1 Yusuke Aoki
A1 Kentaro Miyake
A1 Ryusei Matsuyama
A1 Michael Bouvet
A1 Steven G. Clarke
A1 Itaru Endo
A1 Robert M. Hoffman
YR 2021
UL http://biorxiv.org/content/early/2021/08/03/2020.12.04.412437.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.