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Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells

  • Authors:
    • Lee‑Won Chong
    • Chia‑Ling Tsai
    • Kou‑Ching Yang
    • Chen‑Chung Liao
    • Yi‑Chao Hsu
  • View Affiliations / Copyright

    Affiliations: Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan, R.O.C., Institute of Biomedical Sciences, Mackay Medical College, New Taipei City, Taipei, Taiwan, R.O.C., Proteomics Research Center, National Yang‑Ming University, Taipei, Taiwan, R.O.C.
    Copyright: © Chong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 939-947
    |
    Published online on: May 22, 2020
       https://doi.org/10.3892/mmr.2020.11172
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Abstract

Although non‑alcoholic fatty liver disease (NAFLD) is considered a benign disorder, hepatic steatosis has been proposed to be involved in the tumorigenesis of liver cancer. However, the underlying mechanism for carcinogenesis in fatty liver diseases remains unclear. Cancer stem cells (CSCs) have been hypothesized to serve a key role in tumorigenesis. Tumor formation begins with a subset of heterogeneous cells that share properties with stem cells, such as self‑renewal and undifferentiated properties. Our previous study reported that the saturated fatty acid palmitate (PA) significantly enhanced the CSC properties of the HepG2 human liver cancer cell line; however, its underlying mechanisms are unknown. In the present study, a proteomic approach was used to investigate the palmitoylation of proteins in HepG2 CSCs. CSC behavior was induced in HepG2 cells via 200 µM PA. Proteomic analysis was performed to identify post‑transcriptional modifications of proteins in HepG2 CSCs in response to PA treatment. The present study identified proteins modified by palmitoylation in HepG2 CSC spheres formed following PA treatment. It was therefore hypothesized that palmitoylation may be crucial for CSC sphere formation. Furthermore, the present study demonstrated that two palmitoylation inhibitors, tunicamycin (5, 10 and 25 µg/ml) and 2‑bromohexadecanoic acid (25, 50 and 150 µM), significantly decreased CSC sphere formation without affecting cell viability. An association was identified between sphere formation capacity and tumor‑initiating capacity of CSCs. The results of the present study demonstrated that protein palmitoylation may influence the PA‑induced CSC tumor‑initiating capacity, and that the inhibition of palmitoylation may be a suitable chemopreventive strategy for treating patients with NAFLD.
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1 

Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L and Wymer M: Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes. Hepatology. 64:73–84. 2016. View Article : Google Scholar : PubMed/NCBI

2 

Younossi Z, Tacke F, Arrese M, Chander Sharma B, Mostafa I, Bugianesi E, Wai-Sun Wong V, Yilmaz Y, George J, Fan J and Vos MB: Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Hepatology. 69:2672–2682. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Angulo P and Lindor KD: Treatment of non-alcoholic steatohepatitis. Best Pract Res Clin Gastroenterol. 16:797–810. 2002. View Article : Google Scholar : PubMed/NCBI

4 

Malaguarnera M, Di Rosa M, Nicoletti F and Malaguarnera L: Molecular mechanisms involved in NAFLD progression. J Mol Med (Berl). 87:679–695. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Leamy AK, Egnatchik RA and Young JD: Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res. 52:165–174. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Cao L, Zhou Y, Zhai B, Liao J, Xu W, Zhang R, Li J, Zhang Y, Chen L, Qian H, et al: Sphere-forming cell subpopulations with cancer stem cell properties in human hepatoma cell lines. BMC Gastroenterol. 11:712011. View Article : Google Scholar : PubMed/NCBI

7 

Huang P, Qiu J, Li B, Hong J, Lu C, Wang L, Wang J, Hu Y, Jia W and Yuan Y: Role of Sox2 and Oct4 in predicting survival of hepatocellular carcinoma patients after hepatectomy. Clin Biochem. 44:582–589. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Sun C, Sun L, Li Y, Kang X, Zhang S and Liu Y: Sox2 expression predicts poor survival of hepatocellular carcinoma patients and it promotes liver cancer cell invasion by activating Slug. Med Oncol. 30:5032013. View Article : Google Scholar : PubMed/NCBI

9 

Yin X, Li YW, Zhang BH, Ren ZG, Qiu SJ, Yi Y and Fan J: Coexpression of stemness factors Oct4 and Nanog predict liver resection. Ann Surg Oncol. 19:2877–2887. 2012. View Article : Google Scholar : PubMed/NCBI

10 

Ma XL, Sun YF, Wang BL, Shen MN, Zhou Y, Chen JW, Hu B, Gong ZJ, Zhang X, Cao Y, et al: Sphere-forming culture enriches liver cancer stem cells and reveals Stearoyl-CoA desaturase 1 as a potential therapeutic target. BMC Cancer. 19:7602019. View Article : Google Scholar : PubMed/NCBI

11 

Stafman LL, Williams AP, Garner EF, Aye JM, Stewart JE, Yoon KJ, Whelan K and Beierle EA: Targeting PIM kinases affects maintenance of CD133 tumor cell population in hepatoblastoma. Transl Oncol. 12:200–208. 2019. View Article : Google Scholar : PubMed/NCBI

12 

Maehara O, Ohnishi S, Asano A, Suda G, Natsuizaka M, Nakagawa K, Kobayashi M, Sakamoto N and Takeda H: Metformin regulates the expression of CD133 through the AMPK-CEBPβ pathway in hepatocellular carcinoma cell lines. Neoplasia. 21:545–556. 2019. View Article : Google Scholar : PubMed/NCBI

13 

Chen WC, Chang YS, Hsu HP, Yen MC, Huang HL, Cho CY, Wang CY, Weng TY, Lai PT, Chen CS, et al: Therapeutics targeting CD90-integrin-AMPK-CD133 signal axis in liver cancer. Oncotarget. 6:42923–42937. 2015. View Article : Google Scholar : PubMed/NCBI

14 

He J, Liu Y, Zhu T, Zhu J, Dimeco F, Vescovi AL, Heth JA, Muraszko KM, Fan X and Lubman DM: CD90 is identified as a candidate marker for cancer stem cells in primary high-grade gliomas using tissue microarrays. Mol Cell Proteomics. 11:M111.010744. 2012. View Article : Google Scholar

15 

Zhang K, Che S, Pan C, Su Z, Zheng S, Yang S, Zhang H, Li W, Wang W and Liu J: The SHH/Gli axis regulates CD90-mediated liver cancer stem cell function by activating the IL6/JAK2 pathway. J Cell Mol Med. 22:3679–3690. 2018. View Article : Google Scholar : PubMed/NCBI

16 

Wei S, Liu K, He Q, Gao Y and Shen L: PES1 is regulated by CD44 in liver cancer stem cells via miR-105-5p. FEBS Lett. 593:1777–1786. 2019. View Article : Google Scholar : PubMed/NCBI

17 

Yamashita T, Honda M, Nakamoto Y, Baba M, Nio K, Hara Y, Zeng SS, Hayashi T, Kondo M, Takatori H, et al: Discrete nature of EpCAM+ and CD90+ cancer stem cells in human hepatocellular carcinoma. Hepatology. 57:1484–1497. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Christ B, Stock P and Dollinger MM: CD13: Waving the flag for a novel cancer stem cell target. Hepatology. 53:1388–1390. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Reynolds BA and Weiss S: Clonal and population analyses demonstrate that an EGF-responsive mammalian embryonic CNS precursor is a stem cell. Dev Biol. 175:1–13. 1996. View Article : Google Scholar : PubMed/NCBI

20 

Dontu G, Abdallah WM, Foley JM, Jackson KW, Clarke MF, Kawamura MJ and Wicha MS: In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev. 17:1253–1270. 2003. View Article : Google Scholar : PubMed/NCBI

21 

Suzuki A, Oyama K, Fukao K, Nakauchi H and Taniguchi H: Establishment of clonal colony-forming assay system for pancreatic stem/progenitor cells. Cell Transplant. 11:451–453. 2002. View Article : Google Scholar : PubMed/NCBI

22 

Shi X, Gipp J and Bushman W: Anchorage-independent culture maintains prostate stem cells. Dev Biol. 312:396–406. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA and Daidone MG: Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res. 65:5506–5511. 2005. View Article : Google Scholar : PubMed/NCBI

24 

Gou S, Liu T, Wang C, Yin T, Li K, Yang M and Zhou J: Establishment of clonal colony-forming assay for propagation of pancreatic cancer cells with stem cell properties. Pancreas. 34:429–435. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Rappa G, Mercapide J, Anzanello F, Prasmickaite L, Xi Y, Ju J, Fodstad O and Lorico A: Growth of cancer cell lines under stem cell-like conditions has the potential to unveil therapeutic targets. Exp Cell Res. 314:2110–2122. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Wobser H, Dorn C, Weiss TS, Amann T, Bollheimer C, Büttner R, Schölmerich J and Hellerbrand C: Lipid accumulation in hepatocytes induces fibrogenic activation of hepatic stellate cells. Cell Res. 19:996–1005. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Chong LW, Chou RH, Liao CC, Lee TF, Lin Y, Yang KC and Hsu YC: Saturated fatty acid induces cancer stem cell-like properties in human hepatoma cells. Cell Mol Biol (Noisy-le-Grand). 61:85–91. 2015.PubMed/NCBI

28 

Anderson AM and Ragan MA: Palmitoylation: A protein S-acylation with implications for breast cancer. NPJ Breast Cancer. 2:160282016. View Article : Google Scholar : PubMed/NCBI

29 

Yang MH, Liao CC, Hung JH, Lai XT, Yen CH and Chen YA: Utilizing proteomic approach to identify nuclear translocation related serine kinase phosphorylation site of GNMT as downstream effector for benzo[a]pyrene. J Food Drug Anal. 27:603–609. 2019. View Article : Google Scholar : PubMed/NCBI

30 

Chong LW, Hsu YC, Lee TF, Lin Y, Chiu YT, Yang KC, Wu JC and Huang YT: Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells. BMC Gastroenterol. 15:222015. View Article : Google Scholar : PubMed/NCBI

31 

Alessio N, Del Gaudio S, Capasso S, Di Bernardo G, Cappabianca S, Cipollaro M, Peluso G and Galderisi U: Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process. Oncotarget. 6:8155–8166. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Buckley BJ and Whorton AR: Tunicamycin increases intracellular calcium levels in bovine aortic endothelial cells. Am J Physiol. 273:C1298–C1305. 1997. View Article : Google Scholar : PubMed/NCBI

33 

Sobocińska J, Roszczenko-Jasińska P, Zaręba-Kozioł M, Hromada-Judycka A, Matveichuk OV, Traczyk G, Łukasiuk K and Kwiatkowska K: Lipopolysaccharide upregulates palmitoylated enzymes of the phosphatidylinositol cycle: An insight from proteomic studies. Mol Cell Proteomics. 17:233–254. 2018. View Article : Google Scholar : PubMed/NCBI

34 

Patterson SI and Skene JH: Novel inhibitory action of tunicamycin homologues suggests a role for dynamic protein fatty acylation in growth cone-mediated neurite extension. J Cell Biol. 124:521–536. 1994. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Chong LW, Tsai CL, Yang KC, Liao CC and Hsu YC: Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells. Mol Med Rep 22: 939-947, 2020.
APA
Chong, L., Tsai, C., Yang, K., Liao, C., & Hsu, Y. (2020). Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells. Molecular Medicine Reports, 22, 939-947. https://doi.org/10.3892/mmr.2020.11172
MLA
Chong, L., Tsai, C., Yang, K., Liao, C., Hsu, Y."Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells". Molecular Medicine Reports 22.2 (2020): 939-947.
Chicago
Chong, L., Tsai, C., Yang, K., Liao, C., Hsu, Y."Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells". Molecular Medicine Reports 22, no. 2 (2020): 939-947. https://doi.org/10.3892/mmr.2020.11172
Copy and paste a formatted citation
x
Spandidos Publications style
Chong LW, Tsai CL, Yang KC, Liao CC and Hsu YC: Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells. Mol Med Rep 22: 939-947, 2020.
APA
Chong, L., Tsai, C., Yang, K., Liao, C., & Hsu, Y. (2020). Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells. Molecular Medicine Reports, 22, 939-947. https://doi.org/10.3892/mmr.2020.11172
MLA
Chong, L., Tsai, C., Yang, K., Liao, C., Hsu, Y."Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells". Molecular Medicine Reports 22.2 (2020): 939-947.
Chicago
Chong, L., Tsai, C., Yang, K., Liao, C., Hsu, Y."Targeting protein palmitoylation decreases palmitate‑induced sphere formation of human liver cancer cells". Molecular Medicine Reports 22, no. 2 (2020): 939-947. https://doi.org/10.3892/mmr.2020.11172
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