Sirt1 is a tumor promoter in lung adenocarcinoma

Chen,Xue; Hokka,Daisuke; Maniwa,Yoshimasa; Ohbayashi,Chiho; Itoh,Tomoo; Hayashi,Yoshitake

doi:10.3892/ol.2014.2057

Sirt1 is a tumor promoter in lung adenocarcinoma

Authors:
- Xue Chen
- Daisuke Hokka
- Yoshimasa Maniwa
- Chiho Ohbayashi
- Tomoo Itoh
- Yoshitake Hayashi
View Affiliations

Affiliations: Division of Molecular Medicine and Medical Genetics, Department of Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Division of Thoracic Surgery, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan, Department of Pathology, Nara Medical University, Kashihara, Nara 634‑8522, Japan, Department of Diagnostic Pathology, Kobe University Graduate School of Medicine, Kobe, Hyogo 650‑0017, Japan
Published online on: April 10, 2014 https://doi.org/10.3892/ol.2014.2057
Pages: 387-393

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Sirtuin 1 (Sirt1) is a nicotinamide adenine dinucleotide‑dependent class III histone deacetylase. It reportedly can repress cellular apoptosis and senescence to affect DNA repair, stress response and aging. Notably, previous data have indicated that Sirt1 is both a tumor promoter and a tumor suppressor in tumorigenesis. However, Sirt1 expression in primary lung adenocarcinoma remains unknown. Immunohistochemical staining was performed to investigate Sirt1 expression in cancer cells in 125 consecutive resected cases of primary lung adenocarcinoma. Sirt1 expression was found to be increased in 26 (20.8%) of the 125 cases, which correlated significantly with five clinicopathological factors: Ki67 index, hypoxia‑inducible factor 1 (HIF1) molecule expression, tumor‑node‑metastasis (TNM) classification, pulmonary vein invasion and lymphatic duct invasion. In the Sirt1‑positive expression group, Sirt1 expression correlated with a higher Ki67 index and higher TNM classification, particularly for lymph node invasion and metastasis, and with a higher number of pulmonary vein invasion and lymphatic duct invasion. Additionally, a negative correlation was identified between HIF1‑positive expression and Sirt1‑negative expression. These results indicate that Sirt1 overexpression plays a promotional role in tumorigenesis and is closely associated with invasion and metastasis and, thus, it may be associated with prognosis.

View Figures

View References

1	Jeyapalan JC and Sedivy JM: Cellular senescence and organismal aging. Mech Ageing Dev. 129:467–474. 2008.
2	Krtolica A and Campisi J: Cancer and aging: a model for the cancer promoting effects of the aging stroma. Int J Biochem Cell Biol. 34:1401–1414. 2002.
3	Lombard DB, Chua KF, Mostoslavsky R, et al: DNA repair, genome stability, and aging. Cell. 120:497–512. 2005.
4	Jung-Hynes B and Ahmad N: Role of p53 in the anti-proliferative effects of Sirt1 inhibition in prostate cancer cells. Cell Cycle. 8:1478–1483. 2009.
5	Yi J and Luo J: SIRT1 and p53, effect on cancer, senescence and beyond. Biochim Biophys Acta. 1804:1684–1689. 2010.
6	Liu T, Liu PY and Marshall GM: The critical role of the class III histone deacetylase SIRT1 in cancer. Cancer Res. 69:1702–1705. 2009.
7	Fang Y and Nicholl MB: Sirtuin 1 in malignant transformation: friend or foe? Cancer Lett. 306:10–14. 2011.
8	Tseng RC, Lee CC, Hsu HS, et al: Distinct HIC1-SIRT1-p53 loop deregulation in lung squamous carcinoma and adenocarcinoma patients. Neoplasia. 11:763–770. 2009.
9	Deng CX: SIRT1, is it a tumor promoter or tumor suppressor? Int J Biol Sci. 5:147–152. 2009.
10	Kim JE, Chen J and Lou Z: DBC1 is a negative regulator of SIRT1. Nature. 451:583–586. 2008.
11	Abdelmohsen K, Pullmann R Jr, Lal A, et al: Phosphorylation of HuR by Chk2 regulates SIRT1 expression. Mol Cell. 25:543–557. 2007.
12	Kim EJ, Kho JH, Kang MR and Um SJ: Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. Mol Cell. 28:277–290. 2007.
13	Ford J, Jiang M and Milner J: Cancer-specific functions of SIRT1 enable human epithelial cancer cell growth and survival. Cancer Res. 65:10457–10463. 2005.
14	Huffman DM, Grizzle WE, Bamman MM, et al: SIRT1 is significantly elevated in mouse and human prostate cancer. Cancer Res. 67:6612–6618. 2007.
15	Bradbury C, Khanim FL, Hayden R, et al: Histone deacetylases in acute myeloid leukaemia show a distinctive pattern of expression that changes selectively in response to deacetylase inhibitors. Leukemia. 19:1751–1759. 2005.
16	Kabra N, Li Z, Chen L, et al: SirT1 is an inhibitor of proliferation and tumor formation in colon cancer. J Biol Chem. 284:18210–18217. 2009.
17	Yeung F, Hoberg JE, Ramsey CS, et al: Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23:2369–2380. 2004.
18	Tang Y, Zhao W, Chen Y, Zhao Y and Gu W: Acetylation is indispensable for p53 activation. Cell. 133:612–626. 2008.
19	Wang C, Chen L, Hou X, et al: Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol. 8:1025–1031. 2006.
20	Stünkel W, Peh BK, Tan YC, et al: Function of the SIRT1 protein deacetylase in cancer. Biotechnol J. 2:1360–1368. 2007.
21	Brunet A, Sweeney LB, Sturgill JF, et al: Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 303:2011–2015. 2004.
22	Kobayashi Y, Furukawa-Hibi Y, Chen C, et al: SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress. Int J Mol Med. 16:237–243. 2005.
23	An BS, Tavera-Mendoza LE, Dimitrov V, et al: Stimulation of Sirt1-regulated FoxO protein function by the ligand-bound vitamin D receptor. Mol Cell Biol. 30:4890–4900. 2010.
24	Hokka D, Maniwa Y, Tane S, et al: Psf3 is a prognostic biomarker in lung adenocarcinoma. Lung Cancer. 79:77–82. 2013.
25	Satoh N, Maniwa Y, Bermudez VP, Nishimura K, Nishio W, Yoshimura M, et al: Oncogenic hosphatase Wip1 is a novel prognostic marker for lung adenocarcinoma patient survival. Cancer Sci. 102:1101–1106. 2011.
26	Nakai R, Maniwa Y, Tanaka Y, Nishio W, Yoshimura M, Okita Y, et al: Overexpression of Necl-5 correlates with unfavorable prognosis in patients with lung adenocarcinoma. Cancer Sci. 101:1326–1330. 2010.
27	Ke Q and Costa M: Hypoxia-inducible factor-1 (HIF-1). Mol Pharmacol. 70:1469–1480. 2006.
28	Volm M and Koomägi R: Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and proliferation in lung cancer. Anticancer Res. 20:1527–1533. 2000.
29	Greijer AE and van der Wall E: The role of hypoxia inducible factor 1 (HIF-1) in hypoxia induced apoptosis. J Clin Pathol. 57:1009–1014. 2004.
30	Halliwell B: Oxidative stress and cancer: have we moved forward? Biochem J. 401:1–11. 2007.
31	Brooks CL and Gu W: How does SIRT1 affect metabolism, senescence and cancer? Nat Rev Cancer. 9:123–128. 2009.