TY - JOUR
T1 - Tumour-suppressive function of SIRT4 in human colorectal cancer
AU - Miyo, M.
AU - Yamamoto, H.
AU - Konno, M.
AU - Colvin, H.
AU - Nishida, N.
AU - Koseki, J.
AU - Kawamoto, K.
AU - Ogawa, H.
AU - Hamabe, A.
AU - Uemura, M.
AU - Nishimura, J.
AU - Hata, T.
AU - Takemasa, I.
AU - Mizushima, T.
AU - Doki, Y.
AU - Mori, M.
AU - Ishii, H.
N1 - Funding Information:
We thank the members of our laboratories for their fruitful discussions. This work received the following financial support: a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology (to MK, HI, and MM); a Grant-in-Aid from the Ministry of Health, Labor, and Welfare (to MK, HI, and MM); a grant from the Kobayashi Cancer Research Foundation (to HI); a grant from the Princess Takamatsu Cancer Research Fund, Japan (to HI); a grant from the National Institute of Biomedical Innovation (to MK, HI, and MM); and a grant from the Osaka University Drug Discovery Funds (to MK, HI, and MM). Partial support was received from Takeda Science and Medical Research Foundation through institutional endowments (to MM and HI), Princess Takamatsu Cancer Research Fund (to MM and HI), Kobayashi Cancer Research Foundation (to MM and HI), Suzuken Memorial Foundation (to MK), Yasuda Medical Foundation (to NN), Pancreas Research Foundation (to KK), Nakatani Foundation (to HI), and Nakatomi Foundation of Japan (to MK).
Publisher Copyright:
© 2015 Cancer Research UK. All rights reserved.
PY - 2015/7/28
Y1 - 2015/7/28
N2 - Background: SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers.Methods: We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry.Results: SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis.Conclusions: SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
AB - Background: SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers.Methods: We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry.Results: SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis.Conclusions: SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
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U2 - 10.1038/bjc.2015.226
DO - 10.1038/bjc.2015.226
M3 - Article
C2 - 26086877
AN - SCOPUS:84938422833
SN - 0007-0920
VL - 113
SP - 492
EP - 499
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 3
ER -
