Melatonin-induced KiSS1 expression inhibits triple-negative breast cancer cell invasiveness

Kim,Tae‑Hun; Cho,Sung‑Gook

doi:10.3892/ol.2017.6434

Melatonin-induced KiSS1 expression inhibits triple-negative breast cancer cell invasiveness

Authors:
- Tae‑Hun Kim
- Sung‑Gook Cho
View Affiliations

Affiliations: Department of Biotechnology, Korea National University of Transportation, Jeungpyeong, Chungcheongbuk 368‑701, Republic of Korea
Published online on: June 20, 2017 https://doi.org/10.3892/ol.2017.6434
Pages: 2511-2516

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Breast cancer is one of the most common types of cancer in women, and its metastasis increases the risk of mortality. Melatonin, a hormone that regulates the circadian rhythm, has been revealed to inhibit breast cancer growth and metastasis. However, its involvement in highly metastatic triple‑negative breast cancer cells is yet to be elucidated. The present study demonstrated that melatonin inhibited the metastatic abilities of triple‑negative breast cancer cells and prolonged its inhibitory effect via the expression of kisspeptin (KiSS1), which is a suppressor of metastasis. Melatonin at concentrations ranging from 1 nM to 10 µM did not affect the proliferation of metastatic MDA‑MB‑231 and HCC‑70 triple‑negative breast cancer cells. However, melatonin repressed invasiveness in triple‑negative breast cancer cells. Additionally, conditional medium from melatonin‑treated MDA‑MB‑231 cells repressed the invasiveness of triple‑negative breast cancer cells. Melatonin promoted the production of KiSS1, a metastasis suppressor encoded by the KiSS1 gene. In addition, melatonin increased KiSS1 expression via the expression and transcriptional activation of GATA binding protein 3. Silencing of KiSS1 weakened melatonin inhibition of breast cancer cell invasiveness. Therefore, the present study concluded that melatonin activates KiSS1 production in metastatic breast cancer cells, suggesting that melatonin activation of KiSS1 production may regulate the process of breast cancer metastasis.

View Figures

View References

1	Brainard GC, Hanifin JP, Greeson JM, Byrne B, Glickman G, Gerner E and Rollag MD: Action spectrum for melatonin regulation in humans: Evidence for a novel circadian photoreceptor. J Neurosci. 21:6405–6412. 2001.PubMed/NCBI
2	Lerner AB, Case JD and Takahashi Y: Isolation of melatonin and 5-methoxyindole-3-acetic acid from bovine pineal glands. J Biol Chem. 235:1992–1997. 1960.PubMed/NCBI
3	Stehle JH, von Gall C and Korf HW: Melatonin: A clock-output, a clock-input. J Neuroendocrinol. 15:383–389. 2003. View Article : Google Scholar : PubMed/NCBI
4	Hastings MH, Reddy AB and Maywood ES: A clockwork web: Circadian timing in brain and periphery, in health and disease. Nat Rev Neurosci. 4:649–661. 2003. View Article : Google Scholar : PubMed/NCBI
5	Slominski RM, Reiter RJ, Schlabritz-Loutsevitch N, Ostrom RS and Slominski AT: Melatonin membrane receptors in peripheral tissues: Distribution and functions. Mol Cell Endocrinol. 351:152–166. 2012. View Article : Google Scholar : PubMed/NCBI
6	Claustrat B, Brun J and Chazot G: The basic physiology and pathophysiology of melatonin. Sleep Med Rev. 9:11–24. 2005. View Article : Google Scholar : PubMed/NCBI
7	Dubocovich ML, Delagrange P, Krause DN, Sugden D, Cardinali DP and Olcese J: International union of basic and clinical pharmacology. LXXV. Nomenclature, classification, and pharmacology of G protein-coupled melatonin receptors. Pharmacol Rev. 62:343–380. 2010. View Article : Google Scholar : PubMed/NCBI
8	Acuña-Castroviejo D, Escames G, Venegas C, Díaz-Casado ME, Lima-Cabello E, López LC, Rosales-Corral S, Tan DX and Reiter RJ: Extrapineal melatonin: Sources, regulation, and potential functions. Cell Mol Life Sci. 71:2997–3025. 2014. View Article : Google Scholar : PubMed/NCBI
9	Burstein HJ, Polyak K, Wong JS, Lester SC and Kaelin CM: Ductal carcinoma in situ of the breast. N Engl J Med. 350:1430–1441. 2004. View Article : Google Scholar : PubMed/NCBI
10	Pagani O, Senkus E, Wood W, Colleoni M, Cufer T, Kyriakides S, Costa A, Winer EP and Cardoso F; ESO-MBC Task Force, : International guidelines for management of metastatic breast cancer: Can metastatic breast cancer be cured? J Natl Cancer Inst. 102:456–463. 2010. View Article : Google Scholar : PubMed/NCBI
11	Virnig BA, Tuttle TM, Shamliyan T and Kane RL: Ductal carcinoma in situ of the breast: A systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst. 102:170–178. 2010. View Article : Google Scholar : PubMed/NCBI
12	Rabstein S, Harth V, Justenhoven C, Pesch B, Plöttner S, Heinze E, Lotz A, Baisch C, Schiffermann M, Brauch H, et al: Polymorphisms in circadian genes, night work and breast cancer: Results from the GENICA study. Chronobiol Int. 31:1115–1122. 2014. View Article : Google Scholar : PubMed/NCBI
13	Van Dycke KC, Rodenburg W, van Oostrom CT, van Kerkhof LW, Pennings JL, Roenneberg T, van Steeg H and van der Horst GT: Chronically alternating light cycles increase breast cancer risk in mice. Curr Biol. 25:1932–1937. 2015. View Article : Google Scholar : PubMed/NCBI
14	Basler M, Jetter A, Fink D, Seifert B, Kullak-Ublick GA and Trojan A: Urinary excretion of melatonin and association with breast cancer: Meta-analysis and review of the literature. Breast Care (Basel). 9:182–187. 2014. View Article : Google Scholar : PubMed/NCBI
15	Schernhammer ES and Hankinson SE: Urinary melatonin levels and breast cancer risk. J Natl Cancer Inst. 97:1084–1087. 2005. View Article : Google Scholar : PubMed/NCBI
16	Innominato PF, Lim AS, Palesh O, Clemons M, Trudeau M, Eisen A, Wang C, Kiss A, Pritchard KI and Bjarnason GA: The effect of melatonin on sleep and quality of life in patients with advanced breast cancer. Support Care Cancer. 24:1097–1105. 2016. View Article : Google Scholar : PubMed/NCBI
17	Hill SM, Belancio VP, Dauchy RT, Xiang S, Brimer S, Mao L, Hauch A, Lundberg PW, Summers W, Yuan L, et al: Melatonin: An inhibitor of breast cancer. Endocr Relat Cancer. 22:R183–R204. 2015. View Article : Google Scholar : PubMed/NCBI
18	Kumar P and Aggarwal R: An overview of triple-negative breast cancer. Arch Gynecol Obstet. 293:247–269. 2016. View Article : Google Scholar : PubMed/NCBI
19	Oprea-Ilies G, Haus E, Sackett-Lundeen L, Liu Y, McLendon L, Busch R, Adams A and Cohen C: Expression of melatonin receptors in triple negative breast cancer (TNBC) in African American and Caucasian women: Relation to survival. Breast Cancer Res Treat. 137:677–687. 2013. View Article : Google Scholar : PubMed/NCBI
20	Cho SG, Li D, Tan K, Siwko SK and Liu M: KiSS1 and its G-protein-coupled receptor GPR54 in cancer development and metastasis. Cancer Metastasis Rev. 31:585–591. 2012. View Article : Google Scholar : PubMed/NCBI
21	Tena-Sempere M: Roles of kisspeptins in the control of hypothalamic-gonadotropic function: Focus on sexual differentiation and puberty onset. Endocr Dev. 17:52–62. 2010. View Article : Google Scholar : PubMed/NCBI
22	Papaoiconomou E, Lymperi M, Petraki C, Philippou A, Msaouel P, Michalopoulou F, Kafiri G, Vassilakos G, Zografos G and Koutsilieris M: Kiss-1/GPR54 protein expression in breast cancer. Anticancer Res. 34:1401–1407. 2014.PubMed/NCBI
23	Marot D, Bieche I, Aumas C, Esselin S, Bouquet C, Vacher S, Lazennec G, Perricaudet M, Kuttenn F, Lidereau R and de Roux N: High tumoral levels of Kiss1 and G-protein-coupled receptor 54 expression are correlated with poor prognosis of estrogen receptor-positive breast tumors. Endocr Relat Cancer. 14:691–702. 2007. View Article : Google Scholar : PubMed/NCBI
24	Kostadima L, Pentheroudakis G and Pavlidis N: The missing kiss of life: Transcriptional activity of the metastasis suppressor gene KiSS1 in early breast cancer. Anticancer Res. 27:2499–2504. 2007.PubMed/NCBI
25	Stark AM, Tongers K, Maass N, Mehdorn HM and Held-Feindt J: Reduced metastasis-suppressor gene mRNA-expression in breast cancer brain metastases. J Cancer Res Clin Oncol. 131:191–198. 2005. View Article : Google Scholar : PubMed/NCBI
26	Revel FG, Saboureau M, Masson-Pévet M, Pévet P, Mikkelsen JD and Simonneaux V: Kisspeptin mediates the photoperiodic control of reproduction in hamsters. Curr Biol. 16:1730–1735. 2006. View Article : Google Scholar : PubMed/NCBI
27	Gingerich S, Wang X, Lee PK, Dhillon SS, Chalmers JA, Koletar MM and Belsham DD: The generation of an array of clonal, immortalized cell models from the rat hypothalamus: Analysis of melatonin effects on kisspeptin and gonadotropin-inhibitory hormone neurons. Neuroscience. 162:1134–1140. 2009. View Article : Google Scholar : PubMed/NCBI
28	Borin TF, Arbab AS, Gelaleti GB, Ferreira LC, Moschetta MG, Jardim-Perassi BV, Iskander AS, Varma NR, Shankar A, Coimbra VB, et al: Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression. J Pineal Res. 60:3–15. 2016. View Article : Google Scholar : PubMed/NCBI
29	Jardim-Perassi BV, Lourenco MR, Doho GM, Grígolo IH, Gelaleti GB, Ferreira LC, Borin TF, Moschetta MG and de Campos Zuccari DA Pires: Melatonin regulates angiogenic factors under hypoxia in breast cancer cell lines. Anticancer Agents Med Chem. 16:347–358. 2016. View Article : Google Scholar : PubMed/NCBI
30	Jardim-Perassi BV, Arbab AS, Ferreira LC, Borin TF, Varma NR, Iskander AS, Shankar A, Ali MM and de Campos Zuccari DA: Effect of melatonin on tumor growth and angiogenesis in xenograft model of breast cancer. PLoS One. 9:e853112014. View Article : Google Scholar : PubMed/NCBI
31	Mao L, Yuan L, Slakey LM, Jones FE, Burow ME and Hill SM: Inhibition of breast cancer cell invasion by melatonin is mediated through regulation of the p38 mitogen-activated protein kinase signaling pathway. Breast Cancer Res. 12:R1072010. View Article : Google Scholar : PubMed/NCBI
32	Ortiz-López L, Morales-Mulia S, Ramirez-Rodriguez G and Benitez-King G: ROCK-regulated cytoskeletal dynamics participate in the inhibitory effect of melatonin on cancer cell migration. J Pineal Res. 46:15–21. 2009. View Article : Google Scholar : PubMed/NCBI
33	Mao L, Yuan L, Xiang S, Zeringue SB, Dauchy RT, Blask DE, Hauch A and Hill SM: Molecular deficiency (ies) in MT1 melatonin signaling pathway underlies the melatonin-unresponsive phenotype in MDA-MB-231 human breast cancer cells. J Pineal Res. 56:246–253. 2014. View Article : Google Scholar : PubMed/NCBI
34	Bresnick EH, Lee HY, Fujiwara T, Johnson KD and Keles S: GATA switches as developmental drivers. J Biol Chem. 285:31087–31093. 2010. View Article : Google Scholar : PubMed/NCBI
35	Morceau F, Schnekenburger M, Dicato M and Diederich M: GATA-1: Friends, brothers, and coworkers. Ann NY Acad Sci. 1030:537–554. 2004. View Article : Google Scholar : PubMed/NCBI
36	Zheng R and Blobel GA: GATA transcription factors and cancer. Genes Cancer. 1:1178–1188. 2010. View Article : Google Scholar : PubMed/NCBI
37	Naylor MJ and Ormandy CJ: Gata-3 and mammary cell fate. Breast Cancer Res. 9:3022007. View Article : Google Scholar : PubMed/NCBI
38	Kouros-Mehr H, Kim JW, Bechis SK and Werb Z: GATA-3 and the regulation of the mammary luminal cell fate. Curr Opin Cell Biol. 20:164–170. 2008. View Article : Google Scholar : PubMed/NCBI
39	Oh DS, Troester MA, Usary J, Hu Z, He X, Fan C, Wu J, Carey LA and Perou CM: Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol. 24:1656–1664. 2006. View Article : Google Scholar : PubMed/NCBI
40	Engelsen IB, Stefansson IM, Akslen LA and Salvesen HB: GATA3 expression in estrogen receptor alpha-negative endometrial carcinomas identifies aggressive tumors with high proliferation and poor patient survival. Am J Obstet Gynecol. 199:543.e1–e7. 2008. View Article : Google Scholar
41	Demir H, Turna H, Can G and Ilvan S: Clinicopathologic and prognostic evaluation of invasive breast carcinoma molecular subtypes and GATA3 expression. J BUON. 15:774–782. 2010.PubMed/NCBI
42	Cimino-Mathews A, Subhawong AP, Illei PB, Sharma R, Halushka MK, Vang R, Fetting JH, Park BH and Argani P: GATA3 expression in breast carcinoma: Utility in triple-negative, sarcomatoid, and metastatic carcinomas. Hum Pathol. 44:1341–1349. 2013. View Article : Google Scholar : PubMed/NCBI
43	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
44	Pfaffl MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e452001. View Article : Google Scholar : PubMed/NCBI
45	Nocillado JN, Mechaly AS and Elizur A: In silico analysis of the regulatory region of the Yellowtail Kingfish and Zebrafish Kiss and Kiss receptor genes. Fish Physiol Biochem. 39:59–63. 2013. View Article : Google Scholar : PubMed/NCBI
46	Borin TF, Arbab AS, Gelaleti GB, Ferreira LC, Moschetta MG, Jardim-Perassi BV, Iskander AS, Varma NR, Shankar A, Coimbra VB, et al: Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression. J Pineal Res. 60:3–15. 2016. View Article : Google Scholar : PubMed/NCBI
47	Papantoniou K, Pozo OJ, Espinosa A, Marcos J, Castaño-Vinyals G, Basagaña X, Pagès E Juanola, Mirabent J, Martín J, Faro P Such, et al: Increased and mistimed sex hormone production in night shift workers. Cancer Epidemiol Biomarkers Prev. 24:854–863. 2015. View Article : Google Scholar : PubMed/NCBI
48	Stevens RG, Brainard GC, Blask DE, Lockley SW and Motta ME: Breast cancer and circadian disruption from electric lighting in the modern world. CA Cancer J Clin. 64:207–218. 2014. View Article : Google Scholar : PubMed/NCBI
49	Kim NN, Choi YU, Park HS and Choi CY: Kisspeptin regulates the somatic growth-related factors of the cinnamon clownfish Amphiprion melanopus. Comp Biochem Physiol A Mol Integr Physiol. 179:17–24. 2015. View Article : Google Scholar : PubMed/NCBI
50	Alvarado MV, Carrillo M and Felip A: Melatonin-induced changes in kiss/gnrh gene expression patterns in the brain of male sea bass during spermatogenesis. Comp Biochem Physiol A Mol Integr Physiol. 185:69–79. 2015. View Article : Google Scholar : PubMed/NCBI
51	Zhao GY, Li ZY, Zou HL, Hu ZL, Song NN, Zheng MH, Su CJ and Ding YQ: Expression of the transcription factor GATA3 in the postnatal mouse central nervous system. Neurosci Res. 61:420–428. 2008. View Article : Google Scholar : PubMed/NCBI