TY - JOUR
T1 - Enzymes of the one-carbon folate metabolism as anticancer targets predicted by survival rate analysis
AU - Koseki, Jun
AU - Konno, Masamitsu
AU - Asai, Ayumu
AU - Colvin, Hugh
AU - Kawamoto, Koichi
AU - Nishida, Naohiro
AU - Sakai, Daisuke
AU - Kudo, Toshihiro
AU - Satoh, Taroh
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
N1 - Funding Information:
Competing financial interests: Institutional endowments were received partially from Taiho Pharmaceutical Co., Ltd.; Evidence Based Medical (EBM) Research Center; Unitech Co., Ltd.; Yakult Honsha Co., Ltd.; Chugai Co., Ltd.; and Merck Co., Ltd. These funders had no role in the main experimental equipment, supplies expenses, study design, data collection and analysis, decision to publish, or preparation of this manuscript. The authors declare no competing financial interests.
Funding Information:
We would like to thank the members of our laboratories for their fruitful discussion and Drs. Masaaki Miyo and Kozo Noguchi for their support of statistical analysis. This work received the following financial support: grants-in-aid for Scientific Research and P-Direct Grants from the Ministry of Education, Culture, Sports, Science, and Technology (MK, YD, MM, and HI); a grant-in-aid from the Ministry of Health, Labour, and Welfare (MK, HI, and MM); a grant from the Kobayashi Cancer Research Foundation (HI); a grant from the Princess Takamatsu Cancer Research Fund, Japan (HI); a grant from the National Institute of Biomedical Innovation (MK, HI, and MM) and a grant from the Osaka University Drug Discovery Funds (NN, JK, KK, MK, MM, and HI). Partial support was received from Takeda Science and Medical Research Foundation through institutional endowments (MM and HI), Princess Takamatsu Cancer Research Fund (MM and HI), Kobayashi Cancer Research Foundation (MM and HI), Suzuken Memorial Foundation (MK), Pancreas Research Foundation of Japan (KK) and the Nakatomi Foundation (MK).
Publisher Copyright:
© 2017 The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - The significance of mitochondrial metabolism in cancer cells has recently been gaining attention. Among other findings, One-carbon folate metabolism has been reported to be closely associated with cellular characteristics in cancer. To study molecular targets for efficient cancer therapy, we investigated the association between the expressions of genes that code enzymes involved in one-carbon metabolism and survival rate of patients with adenocarcinomas of the colorectum and lung. Patients with high expression of genes that control the metabolic cycle of tetrahydrofolate (THF) in mitochondria, SHMT2, MTHFD2, and ALDH1L2, have a shorter overall survival rate compared with patients with low expression of these genes. Our results revealed that these genes could be novel and more promising anticancer targets than dihydrofolate reductase (DHFR), the current target of drug therapy linked with folate metabolism, suggesting the rationale of drug discovery in cancer medicine.
AB - The significance of mitochondrial metabolism in cancer cells has recently been gaining attention. Among other findings, One-carbon folate metabolism has been reported to be closely associated with cellular characteristics in cancer. To study molecular targets for efficient cancer therapy, we investigated the association between the expressions of genes that code enzymes involved in one-carbon metabolism and survival rate of patients with adenocarcinomas of the colorectum and lung. Patients with high expression of genes that control the metabolic cycle of tetrahydrofolate (THF) in mitochondria, SHMT2, MTHFD2, and ALDH1L2, have a shorter overall survival rate compared with patients with low expression of these genes. Our results revealed that these genes could be novel and more promising anticancer targets than dihydrofolate reductase (DHFR), the current target of drug therapy linked with folate metabolism, suggesting the rationale of drug discovery in cancer medicine.
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U2 - 10.1038/s41598-017-18456-x
DO - 10.1038/s41598-017-18456-x
M3 - Article
C2 - 29321536
AN - SCOPUS:85040466477
SN - 2045-2322
VL - 8
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 303
ER -
