CDC20 contributes to the development of human cutaneous squamous cell carcinoma through the Wnt/β‑catenin signaling pathway

Chu,Zhaowei; Zhang,Xinyue; Li,Qingyan; Hu,Guanglei; Lian,Christine   Guo; Geng,Songmei

doi:10.3892/ijo.2019.4727

CDC20 contributes to the development of human cutaneous squamous cell carcinoma through the Wnt/β‑catenin signaling pathway

Authors:
- Zhaowei Chu
- Xinyue Zhang
- Qingyan Li
- Guanglei Hu
- Christine Guo Lian
- Songmei Geng
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Affiliations: Department of Dermatology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Published online on: February 27, 2019 https://doi.org/10.3892/ijo.2019.4727
Pages: 1534-1544
Copyright: © Chu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cell division cycle 20 (CDC20) is a regulatory molecule and serves critical roles at multiple points of the cell cycle. Recent evidence indicates that CDC20 may serve an oncogenic role in a number of human cancer types. However, the role of CDC20 in primary cutaneous squamous cell carcinoma (cSCC) has not been studied, to the best of our knowledge. The aim of the present study was to investigate whether and how CDC20 is involved in the tumorigenesis of cSCC. The results revealed that CDC20 expression was significantly increased in cSCC tissues and cell lines, and its expression was associated with pathological differentiation. Downregulation of CDC20 inhibited cell proliferation, induced cell cycle arrest, promoted apoptosis and reduced migratory ability through inhibition of the Wnt/β‑catenin signaling pathway. Furthermore, all‑trans‑retinoic acid treatment significantly downregulated CDC20 expression in cSCC. The present results revealed that CDC20 may serve a crucial role in human cSCC, and suggested that CDC20 may be a novel biomarker for the prevention, diagnosis and treatment of cSCC.

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1	Lomas A, Leonardi-Bee J and Bath-Hextall F: A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol. 166:1069–1080. 2012. View Article : Google Scholar : PubMed/NCBI
2	Stratigos A, Garbe C, Lebbe C, Malvehy J, del Marmol V, Pehamberger H, Peris K, Becker JC, Zalaudek I, Saiag P, et al: European Dermatology Forum (EDF); European Association of Dermato-Oncology (EADO); European Organization for Research and Treatment of Cancer (EORTC): Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline. Eur J Cancer. 51:1989–2007. 2015. View Article : Google Scholar : PubMed/NCBI
3	Levine DE, Karia PS and Schmults CD: Outcomes of patients with multiple cutaneous squamous cells carcinomas: A 10-year single institution cohort study. JAMA Dermatol. 151:1220–1225. 2015. View Article : Google Scholar : PubMed/NCBI
4	Schmults CD, Karia PS, Carter JB, Han J and Qureshi AA: Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: A 10-year, single-institution cohort study. JAMA Dermatol. 149:541–547. 2013. View Article : Google Scholar : PubMed/NCBI
5	Karia PS, Han J and Schmults CD: Cutaneous squamous cell carcinoma: Estimated incidence of disease, nodal metastasis, and deaths from disease in the United States, 2012. J Am Acad Dermatol. 68:957–966. 2013. View Article : Google Scholar : PubMed/NCBI
6	Chang L, Zhang Z, Yang J, McLaughlin SH and Barford D: Atomic structure of the APC/C and its mechanism of protein ubiquitination. Nature. 522:450–454. 2015. View Article : Google Scholar : PubMed/NCBI
7	Primorac I and Musacchio A: Panta rhei: The APC/C at steady state. J Cell Biol. 201:177–189. 2013. View Article : Google Scholar : PubMed/NCBI
8	Bharadwaj R and Yu H: The spindle checkpoint, aneuploidy, and cancer. Oncogene. 23:2016–2027. 2004. View Article : Google Scholar : PubMed/NCBI
9	Gayyed MF, El-Maqsoud NM, Tawfiek ER, El Gelany SA and Rahman MF: A comprehensive analysis of CDC20 overexpression in common malignant tumors from multiple organs: Its correlation with tumor grade and stage. Tumour Biol. 37:749–762. 2016. View Article : Google Scholar
10	Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M and Kaji M: Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients. J Surg Oncol. 106:423–430. 2012. View Article : Google Scholar : PubMed/NCBI
11	Ding ZY, Wu HR, Zhang JM, Huang GR and Ji DD: Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int J Clin Exp Pathol. 7:722–727. 2014.PubMed/NCBI
12	Karra H, Repo H, Ahonen I, Löyttyniemi E, Pitkänen R, Lintunen M, Kuopio T, Söderström M and Kronqvist P: Cdc20 and securin overexpression predict short-term breast cancer survival. Br J Cancer. 110:2905–2913. 2014. View Article : Google Scholar : PubMed/NCBI
13	Wu WJ, Hu KS, Wang DS, Zeng ZL, Zhang DS, Chen DL, Bai L and Xu RH: CDC20 overexpression predicts a poor prognosis for patients with colorectal cancer. J Transl Med. 11:1422013. View Article : Google Scholar : PubMed/NCBI
14	Li J, Gao JZ, Du JL, Huang ZX and Wei LX: Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma. Int J Oncol. 45:1547–1555. 2014. View Article : Google Scholar : PubMed/NCBI
15	Yam CH, Fung TK and Poon RY: Cyclin A in cell cycle control and cancer. Cell Mol Life Sci. 59:1317–1326. 2002. View Article : Google Scholar : PubMed/NCBI
16	Rieder CL: Mitosis in vertebrates: The G2/M and M/A transitions and their associated checkpoints. Chromosome Res. 19:291–306. 2011. View Article : Google Scholar : PubMed/NCBI
17	Wolf F, Wandke C, Isenberg N and Geley S: Dose-dependent effects of stable cyclin B1 on progression through mitosis in human cells. EMBO J. 25:2802–2813. 2006. View Article : Google Scholar : PubMed/NCBI
18	Hameetman L, Commandeur S, Bavinck JN, Wisgerhof HC, de Gruijl FR, Willemze R, Mullenders L, Tensen CP and Vrieling H: Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients. BMC Cancer. 13:582013. View Article : Google Scholar : PubMed/NCBI
19	Lambert SR, Mladkova N, Gulati A, Hamoudi R, Purdie K, Cerio R, Leigh I, Proby C and Harwood CA: Key differences identified between actinic keratosis and cutaneous squamous cell carcinoma by transcriptome profiling. Br J Cancer. 110:520–529. 2014. View Article : Google Scholar :
20	Hu G, Liang L, Liu Y, Liu J, Tan X, Xu M, Peng L, Zhai S, Li Q, Chu Z, et al: TWEAK/Fn14 Interaction Confers Aggressive Properties to Cutaneous Squamous Cell Carcinoma. J Invest Dermatol. November 8–2018.Epub ahead of print.
21	Livak KJ and Schmittgen TD: Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods. 25:402–408. 2001. View Article : Google Scholar
22	Rheinwald JG and Beckett MA: Tumorigenic keratinocyte lines requiring anchorage and fibroblast support cultured from human squamous cell carcinomas. Cancer Res. 41:1657–1663. 1981.PubMed/NCBI
23	Que SKT, Zwald FO and Schmults CD: Cutaneous squamous cell carcinoma: Incidence, risk factors, diagnosis, and staging. J Am Acad Dermatol. 78:237–247. 2018. View Article : Google Scholar : PubMed/NCBI
24	Izawa D and Pines J: How APC/C-Cdc20 changes its substrate specificity in mitosis. Nat Cell Biol. 13:223–233. 2011. View Article : Google Scholar : PubMed/NCBI
25	Wang L, Zhang J, Wan L, Zhou X, Wang Z and Wei W: Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Ther. 151:141–151. 2015. View Article : Google Scholar : PubMed/NCBI
26	Geley S, Kramer E, Gieffers C, Gannon J, Peters JM and Hunt T: Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. J Cell Biol. 153:137–148. 2001. View Article : Google Scholar : PubMed/NCBI
27	Shang G, Ma X and Lv G: Cell division cycle 20 promotes cell proliferation and invasion and inhibits apoptosis in osteosarcoma cells. Cell Cycle. 17:43–52. 2018. View Article : Google Scholar :
28	Lim HJ, Dimova NV, Tan MK, Sigoillot FD, King RW and Shi Y: The G2/M regulator histone demethylase PHF8 is targeted for degradation by the anaphase-promoting complex containing CDC20. Mol Cell Biol. 33:4166–4180. 2013. View Article : Google Scholar : PubMed/NCBI
29	Song L and Rape M: Regulated degradation of spindle assembly factors by the anaphase-promoting complex. Mol Cell. 38:369–382. 2010. View Article : Google Scholar : PubMed/NCBI
30	Wan L, Tan M, Yang J, Inuzuka H, Dai X, Wu T, Liu J, Shaik S, Chen G, Deng J, et al: APC(Cdc20) suppresses apoptosis through targeting Bim for ubiquitination and destruction. Dev Cell. 29:377–391. 2014. View Article : Google Scholar : PubMed/NCBI
31	Harley ME, Allan LA, Sanderson HS and Clarke PR: Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J. 29:2407–2420. 2010. View Article : Google Scholar : PubMed/NCBI
32	Ku AT, Miao Q and Nguyen H: Monitoring Wnt/β-Catenin Signaling in Skin. Methods Mol Biol. 1481:127–140. 2016. View Article : Google Scholar
33	Zimmerli D, Cecconi V, Valenta T, Hausmann G, Cantù C, Restivo G, Hafner J, Basler K and van den Broek M: WNT ligands control initiation and progression of human papillomavirus-driven squamous cell carcinoma. Oncogene. 37:3753–3762. 2018. View Article : Google Scholar : PubMed/NCBI
34	Blomberg M, He SY, Harwood C, Arron ST, Demehri S and Green A: Research gaps in the management and prevention of cutaneous squamous cell carcinoma in organ transplant recipients. Br J Dermatol. 177:1225–1233. 2017. View Article : Google Scholar : PubMed/NCBI
35	Que SKT, Zwald FO and Schmults CD: Cutaneous squamous cell carcinoma: Management of advanced and high-stage tumors. J Am Acad Dermatol. 78:249–261. 2018. View Article : Google Scholar : PubMed/NCBI
36	Zhang ML, Tao Y, Zhou WQ, Ma PC, Cao YP, He CD, Wei J and Li LJ: All-trans retinoic acid induces cell-cycle arrest in human cutaneous squamous carcinoma cells by inhibiting the mitogen-activated protein kinase-activated protein 1 pathway. Clin Exp Dermatol. 39:354–360. 2014. View Article : Google Scholar : PubMed/NCBI
37	Riahi RR, Bush AE and Cohen PR: Topical Retinoids: Therapeutic Mechanisms in the Treatment of Photodamaged Skin. Am J Clin Dermatol. 17:265–276. 2016. View Article : Google Scholar : PubMed/NCBI
38	Mukherjee A, Bhattacharyya J, Sagar MV and Chaudhuri A: Liposomally encapsulated CDC20 siRNA inhibits both solid melanoma tumor growth and spontaneous growth of intravenously injected melanoma cells on mouse lung. Drug Deliv Transl Res. 3:224–234. 2013. View Article : Google Scholar : PubMed/NCBI