Pro‑metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts

  • Authors:
    • Shingo Kishi
    • Rina Fujiwara‑Tani
    • Yi Luo
    • Isao Kawahara
    • Kei Goto
    • Kiyomu Fujii
    • Hitoshi Ohmori
    • Chie Nakashima
    • Takamitsu Sasaki
    • Hiroki Kuniyasu
  • View Affiliations

  • Published online on: January 17, 2018     https://doi.org/10.3892/ol.2018.7817
  • Pages: 4423-4426
Metrics: HTML 0 views | PDF 0 views     Cited By (CrossRef): 0 citations

Abstract

Trans fatty acids (TFAs) are risk factors for cardiovascular disorders, and the cancer‑promoting effects of TFAs have been previously reported. The present study examined the effects and signaling of elaidic acid (EA), a TFA, in colorectal cancer (CRC) cells. Oral intake of EA was found to increase metastasis of HT29 human CRC cells. Results indicated that, in the plasma membrane, EA was integrated into cholesterol rafts, which contain epidermal growth factor receptors (EGFR). EA increased nanog and c‑myc, and decreased PGC‑1A through lipid raft‑associated EGFR signaling in HT29 cells. Depletion of cholesterol by methyl‑β‑cyclodextrin treatment abrogated the EA‑induced stemness and oxidative phosphorylation. Simvastatin treatment also abrogated EA‑enhanced tumor growth. These results indicate that EA enhances the stemness by activating EGFR in lipid rafts.

References

1 

Wakao F, Nishimoto H, Kataonoda K, Tsukuma H and Mikami H: Cancer Statistics in Japan. 2013, National Cancer Res Inst, Tokyo. 2013.

2 

Kimura Y, Kono S, Toyomura K, Nagano J, Mizoue T, Moore MA, Mibu R, Tanaka M, Kakeji Y, Maehara Y, et al: Meat, fish and fat intake in relation to subsite-specific risk of colorectal cancer: The Fukuoka colorectal cancer study. Cancer Sci. 98:590–597. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Mizoue T, Tanaka K, Tsuji I, Wakai K, Nagata C, Otani T, Inoue M and Tsugane S; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan, : Alcohol drinking and colorectal cancer risk: An evaluation based on a systematic review of epidemiologic evidence among the Japanese population. Jpn J Clin Oncol. 36:582–597. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Ohmori H, Fujii K, Kadochi Y, Mori S, Nishiguchi Y, Fujiwara R, Kishi S, Sasaki T and Kuniyasu H: Elaidic acid, a trans-fatty acid, enhances the metastasis of colorectal cancer cells. Pathobiology. 84:144–151. 2017. View Article : Google Scholar : PubMed/NCBI

5 

Fujii K, Luo Y, Fujiwara-Tani R, Kishi S, He S, Yang S, Sasaki T, Ohmori H and Kuniyasu H: Pro-metastatic intracellular signaling of the elaidic trans fatty acid. Int J Oncol. 50:85–92. 2017. View Article : Google Scholar : PubMed/NCBI

6 

Molin M, Berstad P, Benth JS, Alexander J, Paulsen JE and Almendingen K: Effect of different degrees of hydrogenated fish oil on intestinal carcinogenesis in Min/+ mice. Anticancer Res. 33:477–483. 2013.PubMed/NCBI

7 

Awad AB: Trans fatty acids in tumor development and the host survival. J Natl Cancer Inst. 67:189–192. 1981.PubMed/NCBI

8 

Tanabe E, Kitayoshi M, Fujii K, Ohmori H, Luo Y, Kadochi Y, Mori S, Fujiwara R, Nishiguchi Y, Sasaki T and Kuniyasu H: Fatty acids inhibit anticancer effects of 5-fluorouracil in mouse cancer cell lines. Oncol Lett. 14:681–686. 2017. View Article : Google Scholar : PubMed/NCBI

9 

Hara T, Kashihara D, Ichimura A, Kimura I, Tsujimoto G and Hirasawa A: Role of free fatty acid receptors in the regulation of energy metabolism. Biochim Biophys Acta. 1841:1292–1300. 2014. View Article : Google Scholar : PubMed/NCBI

10 

Zhang Z, Wang L, Du J, Li Y, Yang H, Li C, Li H and Hu H: Lipid raft localization of epidermal growth factor receptor alters matrix metalloproteinase-1 expression in SiHa cells via the MAPK/ERK signaling pathway. Oncol Lett. 12:4991–4998. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Overmiller AM, McGuinn KP, Roberts BJ, Cooper F, Brennan-Crispi DM, Deguchi T, Peltonen S, Wahl JK III and Mahoney MG: c-Src/Cav1-dependent activation of the EGFR by Dsg2. Oncotarget. 7:37536–37555. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Rao H, Ma LX, Xu TT, Li J, Deng ZY, Fan YW and Li HY: Lipid rafts and Fas/FasL pathway may involve in elaidic acid-induced apoptosis of human umbilical vein endothelial cells. J Agric Food Chem. 62:798–807. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Kuniyasu H, Yano S, Sasaki T, Sasahira T, Sone S and Ohmori H: Colon cancer cell-derived high mobility group 1/amphoterin induces growth inhibition and apoptosis in macrophages. Am J Pathol. 166:751–760. 2005. View Article : Google Scholar : PubMed/NCBI

14 

Kuniyasu H, Oue N, Wakikawa A, Shigeishi H, Matsutani N, Kuraoka K, Ito R, Yokozaki H and Yasui W: Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer. J Pathol. 196:163–170. 2002. View Article : Google Scholar : PubMed/NCBI

15 

Miller T, Yang F, Wise CE, Meng F, Priester S, Munshi MK, Guerrier M, Dostal DE and Glaser SS: Simvastatin stimulates apoptosis in cholangiocarcinoma by inhibition of Rac1 activity. Dig Liver Dis. 43:395–403. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Harvey KA, Walker CL, Xu Z, Whitley P and Siddiqui RA: Trans fatty acids: induction of a pro-inflammatory phenotype in endothelial cells. Lipids. 47:647–657. 2012. View Article : Google Scholar : PubMed/NCBI

17 

Vidgren HM, Louheranta AM, Agren JJ, Schwab US and Uusitupa MI: Divergent incorporation of dietary trans fatty acids in different serum lipid fractions. Lipids. 33:955–962. 1998. View Article : Google Scholar : PubMed/NCBI

18 

Staubach S and Hanisch FG: Lipid rafts: Signaling and sorting platforms of cells and their roles in cancer. Expert Rev Proteomics. 8:263–277. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Rozengurt E: Mitogenic signaling pathways induced by G protein-coupled receptors. J Cell Physiol. 213:589–602. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Postic G, Ghouzam Y, Etchebest C and Gelly JC: TMPL: A database of experimental and theoretical transmembrane protein models positioned in the lipid bilayer. Database (Oxford) 2017. 2017. View Article : Google Scholar

21 

Sancho P, Burgos-Ramos E, Tavera A, Bou Kheir T, Jagust P, Schoenhals M, Barneda D, Sellers K, Campos-Olivas R, Graña O, et al: MYC/PGC-1α balance determines the metabolic phenotype and plasticity of pancreatic cancer stem cells. Cell Metab. 22:590–605. 2015. View Article : Google Scholar : PubMed/NCBI

22 

Scognamiglio R, Cabezas-Wallscheid N, Thier MC, Altamura S, Reyes A, Prendergast ÁM, Baumgärtner D, Carnevalli LS, Atzberger A, Haas S, et al: Myc depletion induces a pluripotent dormant state mimicking diapause. Cell. 164:668–680. 2016. View Article : Google Scholar : PubMed/NCBI

23 

Griner LN, McGraw KL, Johnson JO, List AF and Reuther GW: JAK2-V617F-mediated signalling is dependent on lipid rafts and statins inhibit JAK2-V617F-dependent cell growth. Br J Haematol. 160:177–187. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Irwin ME, Mueller KL, Bohin N, Ge Y and Boerner JL: Lipid raft localization of EGFR alters the response of cancer cells to the EGFR tyrosine kinase inhibitor gefitinib. J Cell Physiol. 226:2316–2328. 2011. View Article : Google Scholar : PubMed/NCBI

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April 2018
Volume 15 Issue 4

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Copy and paste a formatted citation
APA
Kishi, S., Fujiwara‑Tani, R., Luo, Y., Kawahara, I., Goto, K., Fujii, K. ... Kuniyasu, H. (2018). Pro‑metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts. Oncology Letters, 15, 4423-4426. https://doi.org/10.3892/ol.2018.7817
MLA
Kishi, S., Fujiwara‑Tani, R., Luo, Y., Kawahara, I., Goto, K., Fujii, K., Ohmori, H., Nakashima, C., Sasaki, T., Kuniyasu, H."Pro‑metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts". Oncology Letters 15.4 (2018): 4423-4426.
Chicago
Kishi, S., Fujiwara‑Tani, R., Luo, Y., Kawahara, I., Goto, K., Fujii, K., Ohmori, H., Nakashima, C., Sasaki, T., Kuniyasu, H."Pro‑metastatic signaling of the trans fatty acid elaidic acid is associated with lipid rafts". Oncology Letters 15, no. 4 (2018): 4423-4426. https://doi.org/10.3892/ol.2018.7817