Advertisement

Tumor Biology

, Volume 33, Issue 6, pp 2099–2106 | Cite as

SCC-S2 is overexpressed in colon cancers and regulates cell proliferation

  • Zhifeng Miao
  • Tingting Zhao
  • Zhenning Wang
  • Yingying Xu
  • Yongxi Song
  • Jianhua Wu
  • Huimian Xu
Research Article

Abstract

SCC-S2 was recently reported to be overexpressed in various cancers and associated with the malignant behavior of cancer cells. However, the expression of SCC-S2 and its biological roles in colon cancers have not been reported. The aim of this study is to investigate the expression and clinical significance of SCC-S2 in colon cancers and explore its biological function in colon cancer cells. We analyzed the expression pattern of SCC-S2 in 92 colon cancer tissues by immunohistochemistry and found that SCC-S2 was overexpressed in 45 (48.9 %) of 92 colon cancer specimens. There was a significant association between SCC-S2 overexpression and TNM stage (p = 0.0387), lymph node metastasis (p = 0.0219), and proliferation index (p = 0.0279). siRNA knockdown of SCC-S2 expression in CACO2 and HCT116 cells decrease cell proliferation, colony formation, and soft agar colony formation ability. Furthermore, western blot analysis showed that SCC-S2 depletion decreased cyclin D1 and phospho-Rb levels. In conclusion, we demonstrated that SCC-S2 is overexpressed in colon cancers and contributes to malignant cell growth by cyclin D1 and phospho-Rb modulation, which makes SCC-S2 a candidate therapeutic target in colon cancer.

Keywords

SCC-S2 Colon cancer Proliferation Cyclin D1 p-Rb 

Notes

Conflicts of interest

None

References

  1. 1.
    Stat bite: worldwide cervical and uterine cancer incidence and mortality, 2002. J Natl Cancer Inst. 2006;98(15):1031.Google Scholar
  2. 2.
    Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ. Cancer statistics, 2005. CA Cancer J Clin. 2005;55(1):10–30.PubMedCrossRefGoogle Scholar
  3. 3.
    Greenwald P. Colon cancer overview. Cancer. 1992;70(5 Suppl):1206–15.PubMedCrossRefGoogle Scholar
  4. 4.
    Kumar D, Whiteside TL, Kasid U. Identification of a novel tumor necrosis factor-alpha-inducible gene, SCC-S2, containing the consensus sequence of a death effector domain of fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein. J Biol Chem. 2000;275(4):2973–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Patel S, Wang FH, Whiteside TL, Kasid U. Identification of seven differentially displayed transcripts in human primary and matched metastatic head and neck squamous cell carcinoma cell lines: implications in metastasis and/or radiation response. Oral Oncol. 1997;33(3):197–203.PubMedCrossRefGoogle Scholar
  6. 6.
    Horrevoets AJ, Fontijn RD, van Zonneveld AJ, de Vries CJ, ten Cate JW, Pannekoek H. Vascular endothelial genes that are responsive to tumor necrosis factor-alpha in vitro are expressed in atherosclerotic lesions, including inhibitor of apoptosis protein-1, stannin, and two novel genes. Blood. 1999;93(10):3418–31.PubMedGoogle Scholar
  7. 7.
    You Z, Ouyang H, Lopatin D, Polver PJ, Wang CY. Nuclear factor-kappa B-inducible death effector domain-containing protein suppresses tumor necrosis factor-mediated apoptosis by inhibiting caspase-8 activity. J Biol Chem. 2001;276(28):26398–404.PubMedCrossRefGoogle Scholar
  8. 8.
    Woodward MJ, de Boer J, Heidorn S, Hubank M, Kioussis D, Williams O, et al. Tnfaip8 is an essential gene for the regulation of glucocorticoid-mediated apoptosis of thymocytes. Cell Death Differ. 17(2):316–23.Google Scholar
  9. 9.
    Kumar D, Gokhale P, Broustas C, Chakravarty D, Ahmad I, Kasid U. Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells. Oncogene. 2004;23(2):612–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Zhang C, Chakravarty D, Sakabe I, Mewani RR, Boudreau HE, Kumar D, Ahmad I, Kasid UN. Role of SCC-S2 in experimental metastasis and modulation of VEGFR-2, MMP-1, and MMP-9 expression. Mol Ther. 2006;13(5):947–55.PubMedCrossRefGoogle Scholar
  11. 11.
    Dong QZ, Zhao Y, Liu Y, Wang Y, Zhang PX, Jiang GY, et al. Overexpression of SCC-S2 correlates with lymph node metastasis and poor prognosis in patients with non-small-cell lung cancer. Cancer Sci. 101(6):1562–9.Google Scholar
  12. 12.
    Allegra CJ, Paik S, Colangelo LH, Parr AL, Kirsch I, Kim G, Klein P, Johnston PG, Wolmark N, Wieand HS. Prognostic value of thymidylate synthase, Ki-67, and p53 in patients with Dukes’ B and C colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project collaborative study. J Clin Oncol. 2003;21(2):241–50.PubMedCrossRefGoogle Scholar
  13. 13.
    Ignat M, Teletin M, Tisserand J, Khetchoumian K, Dennefeld C, Chambon P, Losson R, Mark M. Arterial calcifications and increased expression of vitamin D receptor targets in mice lacking TIF1alpha. Proc Natl Acad Sci U S A. 2008;105(7):2598–603.PubMedCrossRefGoogle Scholar
  14. 14.
    Knudsen KE, Diehl JA, Haiman CA, Knudsen ES. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene. 2006;25(11):1620–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Roy PG, Thompson AM. Cyclin D1 and breast cancer. Breast. 2006;15(6):718–27.PubMedCrossRefGoogle Scholar
  16. 16.
    Ratschiller D, Heighway J, Gugger M, Kappeler A, Pirnia F, Schmid RA, Borner MM, Betticher DC. Cyclin D1 overexpression in bronchial epithelia of patients with lung cancer is associated with smoking and predicts survival. J Clin Oncol. 2003;21(11):2085–93.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2012

Authors and Affiliations

  • Zhifeng Miao
    • 1
  • Tingting Zhao
    • 1
  • Zhenning Wang
    • 1
  • Yingying Xu
    • 1
  • Yongxi Song
    • 1
  • Jianhua Wu
    • 1
  • Huimian Xu
    • 1
    • 2
  1. 1.Department of General SurgeryFirst Affiliated Hospital of China Medical UniversityShenyangChina
  2. 2.Department of Surgical Oncology and General SurgeryFirst affiliated Hospital of China Medical UniversityShenyang CityChina

Personalised recommendations