The Wnt modulator ICG‑001 mediates the inhibition of nasopharyngeal carcinoma cell migration in vitro via the miR‑150/CD44 axis

Chan,Lai‑Sheung; Man,On‑Ying; Kwok,Hoi‑Hin; Chen,Luo; Chan,King‑Chi; Lung,Hong‑Lok; Ngan,Roger Kai‑Cheong; Wong,Ricky Ngok‑Shun; Lo,Kwok‑Wai; Lee,Anne Wing‑Mui; Tsao,George Sai‑Wah; Kahn,Michael; Lung,Maria Li; Mak,Nai‑Ki

doi:10.3892/ijo.2018.4664

The Wnt modulator ICG‑001 mediates the inhibition of nasopharyngeal carcinoma cell migration in vitro via the miR‑150/CD44 axis

Authors:
- Lai‑Sheung Chan
- On‑Ying Man
- Hoi‑Hin Kwok
- Luo Chen
- King‑Chi Chan
- Hong‑Lok Lung
- Roger Kai‑Cheong Ngan
- Ricky Ngok‑Shun Wong
- Kwok‑Wai Lo
- Anne Wing‑Mui Lee
- George Sai‑Wah Tsao
- Michael Kahn
- Maria Li Lung
- Nai‑Ki Mak
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Affiliations: Department of Biology, Hong Kong Baptist University, Hong Kong, P.R. China, Center for Nasopharyngeal Carcinoma Research, University of Hong Kong, Hong Kong, P.R. China, Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, P.R. China, Department of Molecular Medicine, Beckman Research Institute at City of Hope, Duarte, CA 91010, USA
Published online on: December 12, 2018 https://doi.org/10.3892/ijo.2018.4664
Pages: 1010-1020

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Abstract

The Wnt signaling pathway is known to serve an important role in the control of cell migration. The present study analyzed the mechanisms underlying the in vitro modulation of the migration of nasopharyngeal carcinoma (NPC) cells by the CREB‑binding protein/catenin antagonist and Wnt modulator ICG‑001. The results revealed that ICG‑001‑mediated inhibition of tumor cell migration involved downregulated mRNA and protein expression of the Wnt target gene cluster of differentiation (CD)44. It was also demonstrated that ICG‑001 downregulated the expression of CD44, and this effect was accompanied by restored expression of microRNA (miRNA)‑150 in various NPC cell lines. Using a CD44 3'‑untranslated region luciferase reporter assay, miR‑150 was confirmed to be a novel CD44‑targeting miRNA, which could directly target CD44 and subsequently regulate the migration of NPC cells. The present study provides further insight into the inhibition of tumor cell migration through the modulation of miRNA expression by the Wnt modulator ICG‑001.

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1	Cao SM, Simons MJ and Qian CN: The prevalence and prevention of nasopharyngeal carcinoma in China. Chin J Cancer. 30:114–119. 2011. View Article : Google Scholar : PubMed/NCBI
2	Lee AW, Ma BB, Ng WT and Chan AT: Management of nasopharyngeal carcinoma: Current practice and future perspective. J Clin Oncol. 33:3356–3364. 2015. View Article : Google Scholar : PubMed/NCBI
3	Lun SW, Cheung ST, Cheung PF, To KF, Woo JK, Choy KW, Chow C, Cheung CC, Chung GT, Cheng AS, et al: CD44⁺ cancer stem-like cells in EBV-associated nasopharyngeal carcinoma. PLoS One. 7:e524262012. View Article : Google Scholar
4	Zöller M: CD44: Can a cancer-initiating cell profit from an abundantly expressed molecule? Nat Rev Cancer. 11:254–267. 2011. View Article : Google Scholar : PubMed/NCBI
5	Takebe N, Miele L, Harris PJ, Jeong W, Bando H, Kahn M, Yang SX and Ivy SP: Targeting Notch, Hedgehog, and Wnt pathways in cancer stem cells: Clinical update. Nat Rev Clin Oncol. 12:445–464. 2015. View Article : Google Scholar : PubMed/NCBI
6	Garofalo M and Croce CM: Role of microRNAs in maintaining cancer stem cells. Adv Drug Deliv Rev. 81:53–61. 2015. View Article : Google Scholar :
7	Wang ZM, Du WJ, Piazza GA and Xi Y: MicroRNAs are involved in the self-renewal and differentiation of cancer stem cells. Acta Pharmacol Sin. 34:1374–1380. 2013. View Article : Google Scholar : PubMed/NCBI
8	Ravasio R, Ceccacci E and Minucci S: Self-renewal of tumor cells: Epigenetic determinants of the cancer stem cell phenotype. Curr Opin Genet Dev. 36:92–99. 2016. View Article : Google Scholar : PubMed/NCBI
9	Avgustinova A and Benitah SA: The epigenetics of tumour initiation: Cancer stem cells and their chromatin. Curr Opin Genet Dev. 36:8–15. 2016. View Article : Google Scholar : PubMed/NCBI
10	Muñoz P, Iliou MS and Esteller M: Epigenetic alterations involved in cancer stem cell reprogramming. Mol Oncol. 6:620–636. 2012. View Article : Google Scholar : PubMed/NCBI
11	Chan KC, Chan LS, Ip JC, Lo C, Yip TT, Ngan RK, Wong RN, Lo KW, Ng WT, Lee AW, et al: Therapeutic targeting of CBP/β-catenin signaling reduces cancer stem-like population and synergistically suppresses growth of EBV-positive nasopharyngeal carcinoma cells with cisplatin. Sci Rep. 5:99792015. View Article : Google Scholar
12	Busson P, Ganem G, Flores P, Mugneret F, Clausse B, Caillou B, Braham K, Wakasugi H, Lipinski M and Tursz T: Establishment and characterization of three transplantable EBV-containing nasopharyngeal carcinomas. Int J Cancer. 42:599–606. 1988. View Article : Google Scholar : PubMed/NCBI
13	Glaser R, Zhang HY, Yao KT, Zhu HC, Wang FX, Li GY, Wen DS and Li YP: Two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus that were derived from nasopharyngeal carcinomas. Proc Natl Acad Sci USA. 86:9524–9528. 1989. View Article : Google Scholar : PubMed/NCBI
14	Yao KT, Zhang HY, Zhu HC, Wang FX, Li GY, Wen DS, Li YP, Tsai CH and Glaser R: Establishment and characterization of two epithelial tumor cell lines (HNE-1 and HONE-1) latently infected with Epstein-Barr virus and derived from nasopharyngeal carcinomas. Int J Cancer. 45:83–89. 1990. View Article : Google Scholar : PubMed/NCBI
15	Cheng Y, Ho RL, Chan KC, Kan R, Tung E, Lung HL, Yau WL, Cheung AK, Ko JM, Zhang ZF, et al: Anti-angiogenic pathway associations of the 3p21.3 mapped BLU gene in nasopharyngeal carcinoma. Oncogene. 34:4219–4228. 2015. View Article : Google Scholar
16	Chai AW, Cheung AK, Dai W, Ko JM, Ip JC, Chan KW, Kwong DL, Ng WT, Lee AW, Ngan RK, et al: Metastasis-suppressing NID2, an epigenetically-silenced gene, in the pathogenesis of nasopharyngeal carcinoma and esophageal squamous cell carcinoma. Oncotarget. 7:78859–78871. 2016. View Article : Google Scholar : PubMed/NCBI
17	Rahbari R, Sheahan T, Modes V, Collier P, Macfarlane C and Badge RM: A novel L1 retrotransposon marker for HeLa cell line identification. Biotechniques. 46:277–284. 2009. View Article : Google Scholar : PubMed/NCBI
18	Peterson LF, Wang Y, Lo MC, Yan M, Kanbe E and Zhang DE: The multi-functional cellular adhesion molecule CD44 is regulated by the 8;21 chromosomal translocation. Leukemia. 21:2010–2019. 2007. View Article : Google Scholar : PubMed/NCBI
19	Lo MC, Yip TC, Ngan KC, Cheng WW, Law CK, Chan PS, Chan KC, Wong CK, Wong RN, Lo KW, et al: Role of MIF/CXCL8/CXCR2 signaling in the growth of nasopharyngeal carcinoma tumor spheres. Cancer Lett. 335:81–92. 2013. View Article : Google Scholar : PubMed/NCBI
20	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
21	Wielenga VJ, Smits R, Korinek V, Smit L, Kielman M, Fodde R, Clevers H and Pals ST: Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway. Am J Pathol. 154:515–523. 1999. View Article : Google Scholar : PubMed/NCBI
22	Bretscher A, Reczek D and Berryman M: Ezrin: A protein requiring conformational activation to link microfilaments to the plasma membrane in the assembly of cell surface structures. J Cell Sci. 110:3011–3018. 1997.
23	Donatello S, Babina IS, Hazelwood LD, Hill AD, Nabi IR and Hopkins AM: Lipid raft association restricts CD44-ezrin interaction and promotion of breast cancer cell migration. Am J Pathol. 181:2172–2187. 2012. View Article : Google Scholar : PubMed/NCBI
24	Wang S, Mo Y, Midorikawa K, Zhang Z, Huang G, Ma N, Zhao W, Hiraku Y, Oikawa S and Murata M: The potent tumor suppressor miR-497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L. Oncotarget. 6:35893–35907. 2015.PubMed/NCBI
25	Strong MJ, Baddoo M, Nanbo A, Xu M, Puetter A and Lin Z: Comprehensive high-throughput RNA sequencing analysis reveals contamination of multiple nasopharyngeal carcinoma cell lines with HeLa cell genomes. J Virol. 88:10696–10704. 2014. View Article : Google Scholar : PubMed/NCBI
26	Murphy JF, Lennon F, Steele C, Kelleher D, Fitzgerald D and Long AC: Engagement of CD44 modulates cyclooxygenase induction, VEGF generation, and proliferation in human vascular endothelial cells. FASEB J. 19:446–448. 2005. View Article : Google Scholar : PubMed/NCBI
27	Subramaniam V, Vincent IR, Gilakjan M and Jothy S: Suppression of human colon cancer tumors in nude mice by siRNA CD44 gene therapy. Exp Mol Pathol. 83:332–340. 2007. View Article : Google Scholar : PubMed/NCBI
28	Arpin M, Chirivino D, Naba A and Zwaenepoel I: Emerging role for ERM proteins in cell adhesion and migration. Cell Adhes Migr. 5:199–206. 2011. View Article : Google Scholar
29	Lin CH, Hung PH and Chen YJ: CD44 is associated with the aggressive phenotype of nasopharyngeal carcinoma through redox regulation. Int J Mol Sci. 14:13266–13281. 2013. View Article : Google Scholar : PubMed/NCBI
30	Takahashi-Yanaga F and Kahn M: Targeting Wnt signaling: Can we safely eradicate cancer stem cells? Clin Cancer Res. 16:3153–3162. 2010. View Article : Google Scholar : PubMed/NCBI
31	Schmitt M, Metzger M, Gradl D, Davidson G and Orian-Rousseau V: CD44 functions in Wnt signaling by regulating LRP6 localization and activation. Cell Death Differ. 22:677–689. 2015. View Article : Google Scholar :
32	Li T, Chen JX, Fu XP, Yang S, Zhang Z, Chen KhH and Li Y: microRNA expression profiling of nasopharyngeal carcinoma. Oncol Rep. 25:1353–1363. 2011.PubMed/NCBI
33	Bao Y, Guo Y, Li Z, Fang W, Yang Y, Li X, Li Z, Xiong B, Chen Z, Wang J, et al: MicroRNA profiling in Muc2 knockout mice of colitis-associated cancer model reveals epigenetic alterations during chronic colitis malignant transformation. PLoS One. 9:e991322014. View Article : Google Scholar : PubMed/NCBI
34	Machová Poláková K, Lopotová T, Klamová H, Burda P, Trněný M, Stopka T and Moravcová J: Expression patterns of microRNAs associated with CML phases and their disease related targets. Mol Cancer. 10:412011. View Article : Google Scholar : PubMed/NCBI
35	Morris VA, Zhang A, Yang T, Stirewalt DL, Ramamurthy R, Meshinchi S and Oehler VG: MicroRNA-150 expression induces myeloid differentiation of human acute leukemia cells and normal hematopoietic progenitors. PLoS One. 8:e758152013. View Article : Google Scholar : PubMed/NCBI
36	Zhao JJ, Lin J, Lwin T, Yang H, Guo J, Kong W, Dessureault S, Moscinski LC, Rezania D, Dalton WS, et al: microRNA expression profile and identification of miR-29 as a prognostic marker and pathogenetic factor by targeting CDK6 in mantle cell lymphoma. Blood. 115:2630–2639. 2010. View Article : Google Scholar : PubMed/NCBI
37	Wang M, Yang W, Li M and Li Y: Low expression of miR-150 in pediatric intestinal Burkitt lymphoma. Exp Mol Pathol. 96:261–266. 2014. View Article : Google Scholar : PubMed/NCBI
38	Assumpção MB, Moreira FC, Hamoy IG, Magalhães L, Vidal A, Pereira A, Burbano R, Khayat A, Silva A, Santos S, et al: High-throughput miRNA sequencing reveals a field effect in gastric cancer and suggests an epigenetic network mechanism. Bioinform Biol Insights. 9:111–117. 2015. View Article : Google Scholar : PubMed/NCBI
39	Yokobori T, Suzuki S, Tanaka N, Inose T, Sohda M, Sano A, Sakai M, Nakajima M, Miyazaki T, Kato H, et al: miR-150 is associated with poor prognosis in esophageal squamous cell carcinoma via targeting the EMT inducer ZEB1. Cancer Sci. 104:48–54. 2013. View Article : Google Scholar
40	Watanabe A, Tagawa H, Yamashita J, Teshima K, Nara M, Iwamoto K, Kume M, Kameoka Y, Takahashi N, Nakagawa T, et al: The role of microRNA-150 as a tumor suppressor in malignant lymphoma. Leukemia. 25:1324–1334. 2011. View Article : Google Scholar : PubMed/NCBI
41	Chen S, Wang Z, Dai X, Pan J, Ge J, Han X, Wu Z, Zhou X and Zhao T: Re-expression of microRNA-150 induces EBV-positive Burkitt lymphoma differentiation by modulating c-Myb in vitro. Cancer Sci. 104:826–834. 2013. View Article : Google Scholar : PubMed/NCBI
42	Jia Y, Ling M, Zhang L, Jiang S, Sha Y and Zhao R: Downregulation of miR-150 expression by DNA hypermeth-ylation is associated with high 2-hydroxy-(4-methylthio)butanoic acid-induced hepatic cholesterol accumulation in nursery piglets. J Agric Food Chem. 64:7530–7539. 2016. View Article : Google Scholar : PubMed/NCBI
43	Endo K, Kondo S, Shackleford J, Horikawa T, Kitagawa N, Yoshizaki T, Furukawa M, Zen Y and Pagano JS: Phosphorylated ezrin is associated with EBV latent membrane protein 1 in naso-pharyngeal carcinoma and induces cell migration. Oncogene. 28:1725–1735. 2009. View Article : Google Scholar : PubMed/NCBI
44	Wang L, Lin GN, Jiang XL and Lu Y: Expression of ezrin correlates with poor prognosis of nasopharyngeal carcinoma. Tumour Biol. 32:707–712. 2011. View Article : Google Scholar : PubMed/NCBI
45	Tobo T, Hirahashi M, Yao T, Aishima S and Oda Y: Ezrin expression and its phosphorylation in gastric carcinoma with lymphoid stroma and Epstein-Barr virus infection. Mol Clin Oncol. 1:220–224. 2013. View Article : Google Scholar
46	Teo JL and Kahn M: The Wnt signaling pathway in cellular proliferation and differentiation: A tale of two coactivators. Adv Drug Deliv Rev. 62:1149–1155. 2010. View Article : Google Scholar : PubMed/NCBI