Argininosuccinate Synthase 1-Deficiency Enhances the Cell Sensitivity to Arginine through Decreased DEPTOR Expression in Endometrial Cancer

Kenji Ohshima, Satoshi Nojima, Shinichiro Tahara, Masako Kurashige, Yumiko Hori, Kohei Hagiwara, Daisuke Okuzaki, Shinya Oki, Naoki Wada, Jun Ichiro Ikeda, Yoshikatsu Kanai, Eiichi Morii

研究成果: ジャーナルへの寄稿学術誌査読

21 被引用数 (Scopus)

抄録

Argininosuccinate synthetase 1 (ASS1) is a rate-limiting enzyme in arginine biosynthesis. Although ASS1 expression levels are often reduced in several tumors and low ASS1 expression can be a poor prognostic factor, the underlying mechanism has not been elucidated. In this study, we reveal a novel association between ASS1 and migration/invasion of endometrial tumors via regulation of mechanistic target of rapamycin complex (mTORC) 1 signaling. ASS1-knockout cells showed enhanced migration and invasion in response to arginine following arginine starvation. In ASS1-knockout cells, DEPTOR, an inhibitor of mTORC1 signal, was downregulated and mTORC1 signaling was more activated in response to arginine. ASS1 epigenetically enhanced DEPTOR expression by altering the histone methylation. Consistent with these findings, tumor cells at the invasive front of endometrioid carcinoma cases showed lower ASS1 and DEPTOR expression. Our findings suggest that ASS1 levels in each tumor cell are associated with invasion capability in response to arginine within the tumor microenvironment through mTORC1 signal regulation.

本文言語英語
論文番号45504
ジャーナルScientific reports
7
DOI
出版ステータス出版済み - 3月 30 2017

!!!All Science Journal Classification (ASJC) codes

  • 一般

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