Overexpression of MARCKS indicates a poor prognosis of oral squamous cell carcinoma

Li,Chengjing; Xia,Rong; Xue,Haowei; Hu,Yukun; Sun,Ming; Fang,Dongdong; Yang,Wenyu; Xiao,Feng; Hou,Jun

doi:10.3892/ol.2018.9311

Overexpression of MARCKS indicates a poor prognosis of oral squamous cell carcinoma

Authors:
- Chengjing Li
- Rong Xia
- Haowei Xue
- Yukun Hu
- Ming Sun
- Dongdong Fang
- Wenyu Yang
- Feng Xiao
- Jun Hou
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Affiliations: Department of Oral and Maxillofacial Surgery, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China, Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230001, P.R. China
Published online on: August 16, 2018 https://doi.org/10.3892/ol.2018.9311
Pages: 5498-5504

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Abstract

Myristoylated alanine‑rich C kinase substrate (MARCKS) is a protein kinase C substrate functioning in different physiological and pathological mechanisms. Previous studies have suggested that MARCKS is capable of influencing tumorigenesis and progression. However, a limited number of studies are available regarding the role of MARCKS in oral squamous cell carcinoma (OSCC). The present study primarily examined MARCKS expression in the OSCC tissues. Furthermore, increased expression of MARCKS was confirmed in the majority of OSCC tissues. Increased MARCKS expression was correlated with more advanced tumor stages, lymphatic metastasis and a poorer overall patient survival. Further molecular mechanistic examinations revealed that downregulated MARCKS expression inhibited the proliferation and migration of OSCC cells in vitro through interruption of MARCKS expression. In addition, the present study demonstrated that MARCKS aggravated OSCC progression via the phosphoinositide 3‑kinase/protein kinase B pathway. Accordingly, the present study considered MARCKS to be a promoter of OSCC tumorigenesis and progression, with the potential utility as a biomarker of a poor prognosis.

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1	Kademani D: Oral cancer. Mayo Clin Proc. 82:878–887. 2007. View Article : Google Scholar : PubMed/NCBI
2	Ong TK, Murphy C, Smith AB, Kanatas AN and Mitchell DA: Survival after surgery for oral cancer: A 30-year experience. Br J Oral Maxillofac Surg. 55:911–916. 2017. View Article : Google Scholar : PubMed/NCBI
3	Montero PH and Patel SG: Cancer of the oral cavity. Surg Oncol Clin N Am. 24:491–508. 2015. View Article : Google Scholar : PubMed/NCBI
4	Saeed NR and Gold JA: Oral squamous cell carcinoma. BMJ. 308:1372–1373. 1994. View Article : Google Scholar : PubMed/NCBI
5	Wang ZQ, Liu K, Huo ZJ, Li XC, Wang M, Liu P, Pang B and Wang SJ: A cell-targeted chemotherapeutic nanomedicine strategy for oral squamous cell carcinoma therapy. J Nanobiotechnology. 13:632015. View Article : Google Scholar : PubMed/NCBI
6	Xi S and Grandis JR: Gene therapy for the treatment of oral squamous cell carcinoma. J Dent Res. 82:11–16. 2003. View Article : Google Scholar : PubMed/NCBI
7	Lo WY, Tsai MH, Tsai Y, Hua CH, Tsai FJ, Huang SY, Tsai CH and Lai CC: Identification of over-expressed proteins in oral squamous cell carcinoma (OSCC) patients by clinical proteomic analysis. Clin Chim Acta. 376:101–107. 2007. View Article : Google Scholar : PubMed/NCBI
8	Zygogianni AG, Kyrgias G, Karakitsos P, Psyrri A, Kouvaris J, Kelekis N and Kouloulias V: Oral squamous cell cancer: Early detection and the role of alcohol and smoking. Head Neck Oncol. 3:22011. View Article : Google Scholar : PubMed/NCBI
9	Taniguchi H, Manenti S, Suzuki M and Titani K: Myristoylated alanine-rich C kinase substrate (MARCKS), a major protein kinase C substrate, is an in vivo substrate of proline-directed protein kinase(s). A mass spectroscopic analysis of the post-translational modifications. J Biol Chem. 269:18299–18302. 1994.PubMed/NCBI
10	Brooks G: The role of 80K/MARCKS, a specific substrate of protein kinase C, in cell growth and tumour progression. Pigment Cell Res. 7:451–457. 1994. View Article : Google Scholar : PubMed/NCBI
11	Jarboe JS, Anderson JC, Duarte CW, Mehta T, Nowsheen S, Hicks PH, Whitley AC, Rohrbach TD, McCubrey RO, Chiu S, et al: MARCKS regulates growth and radiation sensitivity and is a novel prognostic factor for glioma. Clin Cancer Res. 18:3030–3041. 2012. View Article : Google Scholar : PubMed/NCBI
12	Ulbrich C, Pietsch J, Grosse J, Wehland M, Schulz H, Saar K, Hübner N, Hauslage J, Hemmersbach R, Braun M, et al: Differential gene regulation under altered gravity conditions in follicular thyroid cancer cells: Relationship between the extracellular matrix and the cytoskeleton. Cell Physiol Biochem. 28:185–198. 2011. View Article : Google Scholar : PubMed/NCBI
13	Rombouts K, Carloni V, Mello T, Omenetti S, Galastri S, Madiai S, Galli A and Pinzani M: Myristoylated alanine-rich protein kinase C substrate (MARCKS) expression modulates the metastatic phenotype in human and murine colon carcinoma in vitro and in vivo. Cancer Lett. 333:244–252. 2013. View Article : Google Scholar : PubMed/NCBI
14	Chen X and Rotenberg SA: PhosphoMARCKS drives motility of mouse melanoma cells. Cell Signal. 22:1097–1103. 2010. View Article : Google Scholar : PubMed/NCBI
15	Micallef J, Taccone M, Mukherjee J, Croul S, Busby J, Moran MF and Guha A: Epidermal growth factor receptor variant III-induced glioma invasion is mediated through myristoylated alanine-rich protein kinase C substrate overexpression. Cancer Res. 69:7548–7556. 2009. View Article : Google Scholar : PubMed/NCBI
16	Techasen A, Loilome W, Namwat N, Takahashi E, Sugihara E, Puapairoj A, Miwa M, Saya H and Yongvanit P: Myristoylated alanine-rich C kinase substrate phosphorylation promotes cholangiocarcinoma cell migration and metastasis via the protein kinase C-dependent pathway. Cancer Sci. 101:658–665. 2010. View Article : Google Scholar : PubMed/NCBI
17	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
18	Glaser M, Wanaski S, Buser CA, Boguslavsky V, Rashidzada W, Morris A, Rebecchi M, Scarlata SF, Runnels LW, Prestwich GD, et al: Myristoylated alanine-rich C kinase substrate (MARCKS) produces reversible inhibition of phospholipase C by sequestering phosphatidylinositol 4,5-bisphosphate in lateral domains. J Biol Chem. 271:26187–22693. 1996. View Article : Google Scholar : PubMed/NCBI
19	Ueno E and Rosenberg P: Beta-Bungarotoxin blocks phorbol ester-stimulated phosphorylation of MARCKS, GAP-43 and synapsin I in rat brain synaptosomes. Toxicon. 33:747–762. 1995. View Article : Google Scholar : PubMed/NCBI
20	Woo JH, Wilsbach K, Nordin A, Lorincz A and Gabrielson E: Increased expression of MARCKS in cancer cells represents a potential target for treatment. Cancer Res. 64:2004.PubMed/NCBI
21	Manai M, Thomassin-Piana J, Gamoudi A, Finetti P, Lopez M, Eghozzi R, Ayadi S, Lamine OB, Manai M, Rahal K, et al: MARCKS protein overexpression in inflammatory breast cancer. Oncotarget. 8:6246–6257. 2017. View Article : Google Scholar : PubMed/NCBI
22	Hanada S, Kakehashi A, Nishiyama N, Wei M, Yamano S, Chung K, Komatsu H, Inoue H, Suehiro S and Wanibuchi H: Myristoylated alanine-rich C-kinase substrate as a prognostic biomarker in human primary lung squamous cell carcinoma. Cancer Biomark. 13:289–298. 2013. View Article : Google Scholar : PubMed/NCBI
23	Chen CH, Fong LWR, Yu E, Wu R, Trott JF and Weiss RH: Upregulation of MARCKS in kidney cancer and its potential as a therapeutic target. Oncogene. 36:3588–3598. 2017. View Article : Google Scholar : PubMed/NCBI
24	Hers I, Vincent EE and Tavaré JM: Akt signalling in health and disease. Cell Signal. 10:1515–1527. 2011. View Article : Google Scholar
25	Fruman DA and Rommel C: PI3K and cancer: Lessons, challenges and opportunities. Nat Rev Drug Discov. 13:140–156. 2014. View Article : Google Scholar : PubMed/NCBI
26	Carnero A, Blanco-Aparicio C, Renner O, Link W and Leal JF: The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets. 8:187–198. 2008. View Article : Google Scholar : PubMed/NCBI
27	Ziemba BP, Burke JE, Masson G, Williams RL and Falke JJ: Regulation of PI3K by PKC and MARCKS: Single-molecule analysis of a reconstituted signaling pathway. Biophys J. 110:1811–1825. 2016. View Article : Google Scholar : PubMed/NCBI