Advertisement

Tumor Biology

, Volume 36, Issue 8, pp 6173–6179 | Cite as

Squalene epoxidase (SQLE) promotes the growth and migration of the hepatocellular carcinoma cells

  • Zhenghui Sui
  • Jiahua Zhou
  • Zhangjun Cheng
  • Penhua Lu
Research Article

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignancies with a poor response to chemotherapy. It is very important to identify novel therapeutic targets. Squalene epoxidase (SQLE), one of the rate-limiting enzymes in the cholesterol biosynthesis, recently has been found to be involved in the tumorigenesis. However, its expression profile and function in the progression of HCC remain largely unknown. Here, we found that the expression of SQLE was upregulated in the HCC tissues. Moreover, overexpression of SQLE in HCC cells promoted cell proliferation and migration, while downregulation of SQLE inhibited the tumorigenicity of HCC cells in vitro and in vivo. Mechanistically, SQLE positively regulated the ERK signaling. Taken together, our study suggests that SQLE is a promising therapeutic target in HCC.

Keywords

HCC SQLE ERK Cell proliferation and migration 

Notes

Conflicts of interest

None

References

  1. 1.
    Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics. CA Cancer J Clin. 2014;64(1):9–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Crispo A, Barba M, Malvezzi M, Ciliberto G, Montella M. Mortality trend for liver cancer in a hyperendemic area of hepatitis C virus infection in southern Italy: join-point analysis and comparison with European and Italian data. Eur J Gastroenterol Hepatol. 2014;26(2):245–6.CrossRefPubMedGoogle Scholar
  3. 3.
    Xing S, Li ZW, Tian YF, Zhang LM, Li MQ, Zhou P. Chronic hepatitis virus infection increases the risk of pancreatic cancer: a meta-analysis. Hepatobiliary Pancreat Dis Int. 2013;12(6):575–83.CrossRefPubMedGoogle Scholar
  4. 4.
    Chen WT, Yang CH, Wu CC, Huang YC, Chai CY. Aberrant deleted in liver cancer-1 expression is associated with tumor metastasis and poor prognosis in urothelial carcinoma. APMIS. 2013;121(12):1131–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Houten SM, Schneiders MS, Wanders RJ, Waterham HR. Regulation of isoprenoid/cholesterol biosynthesis in cells from mevalonate kinase-deficient patients. J Biol Chem. 2003;278(8):5736–43.CrossRefPubMedGoogle Scholar
  6. 6.
    Wanders RJ, Romeijn GJ. Cholesterol biosynthesis, peroxisomes and peroxisomal disorders: mevalonate kinase is not only deficient in Zellweger syndrome but also in rhizomelic chondrodysplasia punctata. J Inherit Metab Dis. 1998;21(3):309–12.CrossRefPubMedGoogle Scholar
  7. 7.
    Alberts AW. Lovastatin and simvastatin—inhibitors of HMG CoA reductase and cholesterol biosynthesis. Cardiology. 1990;77 Suppl 4:14–21.CrossRefPubMedGoogle Scholar
  8. 8.
    Tabacik C, Aliau S, Serrou B. Crastes de Paulet A. Post-HMG CoA reductase regulation of cholesterol biosynthesis in normal human lymphocytes: lanosten-3 betal-ol-32-al, a natural inhibitor. Biochem Biophys Res Commun. 1981;101(4):1087–95.CrossRefPubMedGoogle Scholar
  9. 9.
    Seiki S, Frishman WH. Pharmacologic inhibition of squalene synthase and other downstream enzymes of the cholesterol synthesis pathway: a new therapeutic approach to treatment of hypercholesterolemia. Cardiol Rev. 2009;17(2):70–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Trapani L, Segatto M, Ascenzi P, Pallottini V. Potential role of nonstatin cholesterol lowering agents. IUBMB Life. 2011;63(11):964–71.CrossRefPubMedGoogle Scholar
  11. 11.
    Parris TZ, Kovacs A, Hajizadeh S, Nemes S, Semaan M, Levin M, et al. Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas. Oncogenesis. 2014;3:e95.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Souchek JJ, Baine MJ, Lin C, Rachagani S, Gupta S, Kaur S, et al. Unbiased analysis of pancreatic cancer radiation resistance reveals cholesterol biosynthesis as a novel target for radiosensitisation. Br J Cancer. 2014;111(6):1139–49.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Harada T, Chelala C, Crnogorac-Jurcevic T, Lemoine NR. Genome-wide analysis of pancreatic cancer using microarray-based techniques. Pancreatology. 2009;9(1–2):13–24.CrossRefPubMedGoogle Scholar
  14. 14.
    Yuen HF, McCrudden CM, Huang YH, Tham JM, Zhang X, Zeng Q, et al. TAZ expression as a prognostic indicator in colorectal cancer. PLoS One. 2013;8(1):e54211.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Liu Y, Sun W, Zhang K, Zheng H, Ma Y, Lin D, et al. Identification of genes differentially expressed in human primary lung squamous cell carcinoma. Lung Cancer. 2007;56(3):307–17.CrossRefPubMedGoogle Scholar
  16. 16.
    Merrell MA, Wakchoure S, Lehenkari PP, Harris KW, Selander KS. Inhibition of the mevalonate pathway and activation of p38 MAP kinase are independently regulated by nitrogen-containing bisphosphonates in breast cancer cells. Eur J Pharmacol. 2007;570(1–3):27–37.CrossRefPubMedGoogle Scholar
  17. 17.
    Journe F, Laurent G, Chaboteaux C, Nonclercq D, Durbecq V, Larsimont D, et al. Farnesol, a mevalonate pathway intermediate, stimulates MCF-7 breast cancer cell growth through farnesoid-X-receptor-mediated estrogen receptor activation. Breast Cancer Res Treat. 2008;107(1):49–61.CrossRefPubMedGoogle Scholar
  18. 18.
    Clendening JW, Pandyra A, Boutros PC, El Ghamrasni S, Khosravi F, Trentin GA, et al. Dysregulation of the mevalonate pathway promotes transformation. Proc Natl Acad Sci U S A. 2010;107(34):15051–6.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Butt S, Butt T, Jirstrom K, Hartman L, Amini RM, Zhou W, et al. The target for statins, HMG-CoA reductase, is expressed in ductal carcinoma-in situ and may predict patient response to radiotherapy. Ann Surg Oncol. 2014;21(9):2911–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Vinayak S, Schwartz EJ, Jensen K, Lipson J, Alli E, McPherson L, et al. A clinical trial of lovastatin for modification of biomarkers associated with breast cancer risk. Breast Cancer Res Treat. 2013;142(2):389–98.CrossRefPubMedGoogle Scholar
  21. 21.
    Alcaino J, Romero I, Niklitschek M, Sepulveda D, Rojas MC, Baeza M, et al. Functional characterization of the Xanthophyllomyces dendrorhous farnesyl pyrophosphate synthase and geranylgeranyl pyrophosphate synthase encoding genes that are involved in the synthesis of isoprenoid precursors. PLoS One. 2014;9(5):e96626.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Koyama T, Matsubara M, Ogura K. Isoprenoid enzyme systems of silkworm. I. Partial purification of isopentenyl pyrophosphate isomerase, farnesyl pyrophosphate synthetase, and geranylgeranyl pyrophosphate synthetase. J Biochem. 1985;98(2):449–56.CrossRefPubMedGoogle Scholar
  23. 23.
    Miltiadous G, Saougos V, Cariolou M, Elisaf MS. Plasma lipoprotein(a) levels and LDL-cholesterol lowering response to statin therapy in patients with heterozygous familial hypercholesterolemia. Ann Clin Lab Sci. 2006;36(3):353–5.PubMedGoogle Scholar
  24. 24.
    Himbergen TM, van Tits LJ, Voorbij HA, de Graaf J, Stalenhoef AF, Roest M. The effect of statin therapy on plasma high-density lipoprotein cholesterol levels is modified by paraoxonase-1 in patients with familial hypercholesterolaemia. J Intern Med. 2005;258(5):442–9.CrossRefPubMedGoogle Scholar
  25. 25.
    Sawada M, Matsuo M, Hagihara H, Tenda N, Nagayoshi A, Okumura H, et al. Effect of FR194738, a potent inhibitor of squalene epoxidase, on cholesterol metabolism in HepG2 cells. Eur J Pharmacol. 2001;431(1):11–6.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zhenghui Sui
    • 1
  • Jiahua Zhou
    • 1
  • Zhangjun Cheng
    • 1
  • Penhua Lu
    • 2
  1. 1.Department of General Surgery, Zhongda Hospital, School of MedicineSoutheast UniversityNanjinChina
  2. 2.Department of Medical OncologyWuxi People’s Hospital Affiliated Nanjing Medical UniversityWuxiChina

Personalised recommendations