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Global metabolic reprogramming of colorectal cancer occurs at adenoma stage and is induced by MYC

2017; National Academy of Sciences; Volume: 114; Issue: 37 Linguagem: Inglês

10.1073/pnas.1710366114

1091-6490

Kiyotoshi Satoh, Shinichi Yachida, Masahiro Sugimoto, Minoru Oshima, Toshitaka Nakagawa, Shintaro Akamoto, Sho Tabata, Kaori Saitoh, Keiko Kato, Saya Sato, Kaori Igarashi, Yumi Aizawa, Rie Kajino‐Sakamoto, Yasushi Kojima, Teruaki Fujishita, Ayame Enomoto, Akiyoshi Hirayama, Takamasa Ishikawa, Makoto M. Taketo, Yoshio Kushida, Reiji Haba, Keiichi Okano, Masaru Tomita, Yasuyuki Suzuki, Shinji Fukuda, Masahiro Aoki, Tomoyoshi Soga,

ATP Synthase and ATPases Research

Significance Metabolic reprogramming is one of the hallmarks of cancer. However, the underlying mechanisms that regulate cancer metabolism are poorly understood. Here we performed multiomics-based analysis of paired normal–tumor tissues from patients with colorectal cancer, which revealed that the protooncogene protein MYC regulated global metabolic reprogramming of colorectal cancer by modulating 215 metabolic reactions. Importantly, this metabolic reprogramming occurred in a manner not associated with specific gene mutations in colorectal carcinogenesis. For many years, small-molecule or biologic inhibitors of MYC have been required. Here we demonstrate that knockdown of MYC downstream pyrimidine synthesis genes contributes to the suppression of colorectal cancer cell proliferation similar to MYC, and thus pyrimidine synthesis pathways could be potential targets for colorectal cancer therapy.