Generic placeholder image

Current Drug Targets

Author(s): Adrian Bartoszek, Jakub Fichna, Aleksandra Tarasiuk, Agata Binienda, Adam Fabisiak, Julia B. Krajewska, Paula Mosińska, Karolina Niewinna and Maciej Salaga*

DOI: 10.2174/1389450120666191112141901

DownloadDownload PDF Flyer Cite As
Free Fatty Acid Receptors as New Potential Targets in Colorectal Cancer

Page: [1397 - 1404] Pages: 8

  • * (Excluding Mailing and Handling)

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. In developed countries, its mortality remains high, yet the prevalence has established owing to effective screening programs; however due to the westernization of lifestyle, the incidences in many other countries have increased. Although the treatment of CRC has improved in the last few years, the side effects of these approaches cannot be neglected. Recently, members of the family of free fatty acid receptors (FFARs) have become attractive pharmacological targets in many diseases, including asthma; studies also point to their role in carcinogenesis. Here, we discuss current knowledge and future directions in FFAR research related to CRC. Contradictory results of FFARs modulation may derive from the pleiotropic effects of FFAR ligands, receptor distribution and different signal transduction. Hence, we indicate directions of further studies to fully use the potential of FFARs in CRC.

Keywords: Free fatty acids receptors, colorectal cancer, fatty acids, G protein-coupled receptors, cancer, diet.

Graphical Abstract

[1]
Registry PC. Global cancer observatory. Malaysia Cancer Statistics . .2019; Vol. 593: pp. 1-2.http://gco.iarc.fr/today/data/factsheets/populations/458-malaysia-fact-sheets.pdf Internet [cited 2019 May 27
[2]
Weinberg BA, Marshall JL, Salem ME. The growing challenge of, young adults with colorectal cancer oncology (Williston Park) [Internet] .2017; [cited 2019 May 27];. 31(5): 381-9.Available from: http://www.ncbi.nlm.nih.gov/pubmed/28516436
[3]
Center MM, Jemal A, Smith RA, Ward E. Worldwide variations in colorectal cancer Dis Colon Rectum [Internet] .2010; Nov 1 [cited 2019 May 27] ; 53(7): 1099 .Available from: . http://doi.wiley.com/10.3322/caac.20038
[4]
Brenner H, Kloor M, Pox CP. Colorectal cancer. Lancet [Internet] .2014; Apr 26 [cited 2019 May 27] ; 383(9927): 1490-502 . Available from: . https://www.sciencedirect.com/science/article/pii/S0140673613616499?via%3Dihub#bib3
[5]
Krajewska JB, Bartoszek A, Fichna J. New trends in liposome-based drug delivery in colorectal cancer. Mini Rev Med Chem .2019; 19(1): 3-11.
[http://dx.doi.org/10.2174/1389557518666180903150928] [PMID: 30179131]
[6]
Milligan G, Shimpukade B, Ulven T, Hudson BD. Complex pharmacology of free fatty acid receptors. Chem Rev [Internet] .2017; [cited 2018 Jan 6];; 117(1): 67-110. Available from: . http://pubs.acs.org/doi/pdf/10.1021/acs.chemrev.6b00056
[http://dx.doi.org/10.1021/acs.chemrev.6b00056]
[7]
Layden BT, Angueira AR, Brodsky M, Durai V, Lowe WL. Short chain fatty acids and their receptors: New metabolic targets. Transl Res [Internet]. 2013; Mar 1 [cited 2018 Jan 3]; 161(3): 131-40.Available from: . http://www.ncbi.nlm.nih.gov/pubmed/23146568
[8]
Hara T, Kashihara D, Ichimura A, Kimura I, Tsujimoto G, Hirasawa A. Role of free fatty acid receptors in the regulation of energy metabolism. Biochim Biophys Acta - Mol Cell Biol Lipids [Internet] .2014 [cited 2018 Jan 9] ; 1841(9): 1292-300.Available from:. https://ac.els-cdn.com/S1388198114001036/1-s2.0-S13881 98114001036-main.pdf?_tid=f4a2f7a0-f569-11e7-9e7d- 00000aab0f27&acdnat=1515522288_2db4034c5a55502783d4b6bd ca0af250
[http://dx.doi.org/10.1016/j.bbalip.2014.06.002]
[9]
Vinolo MAR, Hirabara SM, Curi R. G-protein-coupled receptors as fat sensors. Curr Opin Clin Nutr Metab Care .2012; 15(2): 112-6.
[http://dx.doi.org/10.1097/MCO.0b013e32834f4598] [PMID: 22234165]
[10]
Kimura I, Inoue D, Maeda T, Hara T, Ichimura A, Miyauchi S, et al. Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41 (GPR41). Proc Natl Acad Sci [Internet] .2011 May 10 [cited 2019 Jun 15]; 108(19): 8030-5.Available from:. http://www.ncbi.nlm.nih.gov/pubmed/21518883
[11]
Alvarez-Curto E, Milligan G. Metabolism meets immunity: The role of free fatty acid receptors in the immune system. Biochem Pharmacol [Internet] . 2016 Aug 15 [cited 2018 Jan 3] . 114:3–13.Available from: . http://www.sciencedirect.com/science/article/pii/S0006295216001842?via%3Dihub
[12]
Tang Y, Chen Y, Jiang H, Robbins GT, Nie D. G-protein-coupled receptor for short-chain fatty acids suppresses colon cancer. Int J Cancer [Internet] . 2011 Feb 15 [cited 2019 Apr 24] ; 128(4): 847-56.Available from:. http://doi.wiley.com/10.1002/ijc.25638
[13]
Mahri S. Al, Ghamdi A, Al, Mohammad S, Aziz MA. . Role of free fatty acid receptor (FFAR3) in Growth and Proliferation of Colorectal Cancer Cell Line. Science Alert .2019; 15(1): 17-22.
[14]
Nandan MO, Yang VW. Genetic and chemical models of colorectal cancer in mice. Curr Colorectal Cancer Rep [Internet] .2010; Mar 10 [cited 2019 May 27] ; 6(2): 51-9. Available from: . http://www.ncbi.nlm.nih.gov/pubmed/2037630310.1007/s11888-010-0046-1
[15]
Sivaprakasam S, Gurav A, Paschall AV, et al. An essential role of Ffar2 (Gpr43) in dietary fibre-mediated promotion of healthy composition of gut microbiota and suppression of intestinal carcinogenesis. Oncogenesis [Internet] .2016 Jun 27 [cited 2019 Apr 24]; ; 5(6): : e238.Available from: . http://www.ncbi.nlm.nih.gov/pubmed/27348268
[16]
Kim M, Friesen L, Park J, Kim HM, Kim CH. Microbial metabolites, short-chain fatty acids, restrain tissue bacterial load, chronic inflammation, and associated cancer in the colon of mice. Eur J Immunol [Internet] .2018 Jul 17 [cited 2019 Apr 24] ; 48(7): 1235-47. Available from: . http://www.ncbi.nlm.nih.gov/pubmed/2964462210.1002/eji.201747122
[17]
Pan P, Oshima K, Huang YW, et al. Loss of FFAR2 promotes colon cancer by epigenetic dysregulation of inflammation suppressors. Int J Cancer 2018; 143(4): 886-96.
[http://dx.doi.org/10.1002/ijc.31366] [PMID: 29524208]
[18]
Mao QD, Zhang W, Zhao K, Cao B, Yuan H, Wei LZ, et al. MicroRNA-455 suppresses the oncogenic function of HDAC2 in human colorectal cancer. Brazilian J Med Biol Res [Internet] 2017 May 18 [cited 2019 Jul 18] ; 50(6): : e6103. Available from: . http://www.ncbi.nlm.nih.gov/pubmed/28538837
[19]
Gao R, Gao Z, Huang L, Qin H. Gut microbiota and colorectal cancer. Eur J Clin Microbiol Infect Dis [Internet] .2017 May [cited 2019 May 27] ; 36(5): 757-69.Available from: . http://www.ncbi.nlm.nih.gov/pubmed/28063002
[http://dx.doi.org/10.1007/s10096-016-2881-8]
[20]
Rezasoltani S, Asadzadeh-Aghdaei H, Nazemalhosseini-Mojarad E, Dabiri H, Ghanbari R, Zali MR. Gut microbiota, epigenetic modification and colorectal cancer. Iran J Microbiol [Internet] .2017 Apr [cited 2019 May 27] ; 9(2): 55-63.Available from: . http://www.ncbi.nlm.nih.gov/pubmed/29213996
[21]
Park Y, Hunter DJ, Spiegelman D, et al. Dietary fiber intake and risk of colorectal cancer. JAMA [Internet] .2005 Dec 14 [cited 2019 May 27] ; 294(22): :2849 .Available from: . http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.294.22.2849
[http://dx.doi.org/10.1001/jama.294.22.2849]
[22]
Kinzler KW, Vogelstein B. Lessons from hereditary colorectal cancer. Cell [Internet] .1996 Oct 18 [cited 2019 May 27] ; 87(2): 159-70.Available from: . http://www.ncbi.nlm.nih.gov/pubmed/8861899
[http://dx.doi.org/10.1016/S0092-8674(00)81333-1]
[23]
Hatanaka H, Tsukui M, Takada S, Kurashina K, Choi YL, Soda M, et al. Identification of transforming activity of free fatty acid receptor 2 by retroviral expression screening. Cancer Sci [Internet] .2010 Jan 1 [cited 2019 Apr 24] ; 101(1): 54-9.Available from: . http://doi.wiley.com/10.1111/j.1349-7006.2009.01348.x
[http://dx.doi.org/10.1111/j.1349-7006.2009.01348.x]
[24]
Zalba S, Contreras AM, Merino M, et al. EGF-liposomes promote efficient EGFR targeting in xenograft colocarcinoma model. Nanomedicine (Lond) .2016; 11(5): 465-77.http://www.futuremedicine.com/doi/10.2217/nnm.15.208
[http://dx.doi.org/10.2217/nnm.15.208] [PMID: 26892017]
[25]
Fujii K, Luo Y, Fujiwara-Tani R, Kishi S, He S, Yang S, et al. Prometastatic intracellular signaling of the elaidic trans fatty acid. Int J Oncol [Internet] .2017 Jan 1 [cited 2019 Apr 24] ; 50(1): 85-92.Available from: . https://www.spandidos-publications.com/10.3892/ijo.2016.3797
[26]
Onishi Y, Otagaki S, Ishimoto K, et al. Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. Exp Cell Res [Internet] .2018 Aug 1 [cited 2019 Feb 18] ; 369(1): 54-60.Available from: . https://www.sciencedirect.com/science/article/pii/S0014482718302660?via%3Dihub
[27]
Wu Q, Wang H, Zhao X, Shi Y, Jin M, Wan B, et al. Identification of G-protein-coupled receptor 120 as a tumor-promoting receptor that induces angiogenesis and migration in human colorectal carcinoma. Oncogene [Internet] 2013 Dec 15 [cited 2018 Oct 30] ; 32(49): 5541-50Available from: . http://www.ncbi.nlm.nih.gov/pubmed/23851494
[28]
Liu Z, Hopkins MM, Zhang Z, et al. Omega-3 fatty acids and other ffa4 agonists inhibit growth factor signaling in human prostate cancer cells. J Pharmacol Exp Ther [Internet] 2015 Feb 1 [cited 2019 Jul 14];; 352(2): 380-94.Available from: . http://www.ncbi.nlm.nih.gov/pubmed/25491146
[29]
Oh DY, Talukdar S, Bae EJ, et al. GPR120 Is an omega-3 fatty acid receptor mediating potent anti-inflammatory and insulin-sensitizing effects. Cell [Internet] 2010 [cited 2018 Oct 17] ; 142(5): 687-98.Available from: . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956412/pdf/nihms-232775.pdf
[http://dx.doi.org/10.1016/j.cell.2010.07.041]
[30]
Calder PC. Polyunsaturated fatty acids, inflammatory processes and inflammatory bowel diseases. Mol Nutr Food Res [Internet] 2008 Aug 1 [cited 2018 Oct 29] ; 52(8): 885-97.Available from: . http://doi.wiley.com/10.1002/mnfr.200700289
[http://dx.doi.org/10.1002/mnfr.200700289]
[31]
Zhang K, Hu Z, Qi H, Shi Z, Chang Y, Yao Q, et al. G-proteincoupled receptors mediate ω-3 PUFAs-inhibited colorectal cancer by activating the Hippo pathway [Internet]. Vol. 7. [cited 2019 Apr 25]. ; Available from: . www.impactjournals.com/oncotarget
[32]
Gutt CN, Brinkmann L, Mehrabi A, et al. ietary omega-3- polyunsaturated fatty acids prevent the development of metastases of colon carcinoma in rat liver. Eur J Nutr [Internet]. .2007 Aug 25 [cited 2019 Jul 18] ; 46(5): 279-85.Available from: . http://link.springer.com/10.1007/s00394-007-0662-y
[http://dx.doi.org/10.1007/s00394-007-0662-y]
[33]
Nakashima C, Shingo K, Fujiwara-Tani R, Luo Y, Kawahara I, Goto K, et al. Expression of long-chain fatty acid receptor GPR40 is associated with cancer progression in colorectal cancer: A retrospective study. Oncol Lett [Internet] .2018 Jun [cited 2019 Apr 24] ; 15(6): 8641-6.Available from: . http://www.ncbi.nlm.nih.gov/pubmed/29805599
[http://dx.doi.org/10.3892/ol.2018.8383]
[34]
Jia HJ, Zhang PJ, Liu YL, Jiang CG, Zhu X, Tian YP. Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer. World J Gastroenterol [Internet] .2016 Feb 28 [cited 2019 Jul 18] ; 22(8): 2524-32.Available from: . http://www.ncbi.nlm. nih.gov/pubmed/26937140
[http://dx.doi.org/10.3748/wjg.v22.i8.2524]