Tumour-suppressive function of SIRT4 in human colorectal cancer

• Published in: British journal of cancer Vol. 113; no. 3; pp. 492 - 499
• Main Authors: Miyo, M, Yamamoto, H, Konno, M, Colvin, H, Nishida, N, Koseki, J, Kawamoto, K, Ogawa, H, Hamabe, A, Uemura, M, Nishimura, J, Hata, T, Takemasa, I, Mizushima, T, Doki, Y, Mori, M, Ishii, H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.07.2015; Nature Publishing Group
• Subjects: 692/699/67/1059/602; 692/699/67/1504/1885; 692/699/67/2327; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cell Movement - genetics; Cell Proliferation - genetics; Colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Disease Progression; Drug Resistance; Epidemiology; Genes, Tumor Suppressor; Glutamine - metabolism; HCT116 Cells; HT29 Cells; Humans; Mitochondrial Proteins - physiology; Molecular Diagnostics; Molecular Medicine; Neoplasm Invasiveness; Oncology; Prognosis; Sirtuins - physiology; Tumor Cells, Cultured; SIRT4; epithelial–mesenchymal transition; colorectal cancer; invasion; tumour suppressor; E-cadherin
• DOI: 10.1038/bjc.2015.226
• ISSN: 0007-0920

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.