Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma cells via the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway

Wang,Xu‑Dong; Wang,Qiang; Chen,Xiao‑Lin; Huang,Jian‑Fei; Yin,Yong; Da,Peng; Wu,Hao

doi:10.3892/mmr.2015.3485

July-2015 Volume 12 Issue 1

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July-2015 Volume 12 Issue 1

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Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma cells via the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway

Authors:
- Xu‑Dong Wang
- Qiang Wang
- Xiao‑Lin Chen
- Jian‑Fei Huang
- Yong Yin
- Peng Da
- Hao Wu
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Affiliations: Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China, Department of Otolaryngology-Head and Neck Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China, Department of Pathology, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226000, P.R. China

Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].
Pages: 865-870
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Published online on: March 13, 2015

https://doi.org/10.3892/mmr.2015.3485
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Abstract

The cell surface glycoprotein Trop2 is overexpressed in various types of epithelial cancer. Laryngeal carcinoma is one of the most common types of head and neck cancer and in a previous study, the expression of Trop2 in laryngeal squamous cell carcinoma (LSCC) was identified as an independent prognostic factor. However, the biological significance of Trop2 in LSCC development remains unclear. In the current study, Trop2 protein expression in fresh LSCC tissue and paracancerous tissue was investigated using western blotting. Trop2 in the Hep2 laryngeal cell line was subsequently suppressed by transfection with small interfering RNA (siRNA). The effects of knockdown of Trop2 on cell viability, migration, invasiveness and ERK/MAPK pathway activity were investigated in the current study. The expression of Trop2 in fresh LSCC tissue was demonstrated to be significantly greater than that in paracancerous tissue. Trop2 expression was also identified to be required for proliferation, migration and invasiveness of Hep2 laryngeal carcinoma cells, as all were blocked by siRNA‑mediated Trop2 inhibition. Notably, the ERK/MAPK signaling pathway and cell cycle factor, cyclin D1, were identified to be suppressed following the knockdown of Trop2 in Hep2 cells. These observations suggest that Trop2 serves an oncogenic role in LSCC and has potential as a therapeutic target.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA. Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
2	Chu EA and Kim YJ: Laryngeal cancer: diagnosis and preoperative work-up. Otolaryngol Clin North Am. 41:673–695. 2008. View Article : Google Scholar : PubMed/NCBI
3	Dirix P, Lambrecht M and Nuyts S: Radiotherapy for laryngeal squamous cell carcinoma: current standards. Expert Rev Anticancer Ther. 10:1461–1469. 2010. View Article : Google Scholar : PubMed/NCBI
4	Tsujikawa M, Kurahashi H, Tanaka T, et al: Identification of the gene responsible for gelatinous drop-like corneal dystrophy. Nat Genet. 21:420–423. 1999. View Article : Google Scholar : PubMed/NCBI
5	Calabrese G, Crescenzi C, Morizio E, Palka G, Guerra E and Alberti S: Assignment of TACSTD1 (alias TROP1, M4S1) to human chromosome 2p21 and refinement of mapping of TACSTD2 (alias TROP2, M1S1) to human chromosome 1p32 by in situ hybridization. Cytogenet Cell Genet. 92:164–165. 2001. View Article : Google Scholar : PubMed/NCBI
6	Nakanishi H, Taccioli C, Palatini J, et al: Loss of miR-125b-1 contributes to head and neck cancer development by dysregu-lating TACSTD2 and MAPK pathway. Oncogene. 33:702–712. 2014. View Article : Google Scholar
7	Cubas R, Zhang S, Li M, Chen C and Yao Q: Trop2 expression contributes to tumor pathogenesis by activating the ERK MAPK pathway. Mol Cancer. 9:2532010. View Article : Google Scholar : PubMed/NCBI
8	Kapoor S: TROP2 expression and its evolving role in tumor pathogenesis in systemic tumors. Tumour Biol. 34:1967–1968. 2013. View Article : Google Scholar
9	Fong D, Moser P, Krammel C, et al: High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer. 99:1290–1295. 2008. View Article : Google Scholar : PubMed/NCBI
10	Fong D, Spizzo G, Gostner JM, et al: TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol. 21:186–191. 2008.
11	Fang YJ, Lu ZH, Wang GQ, et al: Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. Int J Colorectal Dis. 24:875–884. 2009. View Article : Google Scholar : PubMed/NCBI
12	Liu T, Liu Y, Bao X, Tian J and Yang X: Overexpression of TROP2 predicts poor prognosis of patients with cervical cancer and promotes the proliferation and invasion of cervical cancer cells by regulating ERK signaling pathway. PLoS One. 8:e758642013. View Article : Google Scholar : PubMed/NCBI
13	Wu H, Xu H, Zhang S, et al: Potential therapeutic target and independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma. Head Neck. 35:1373–1378. 2013.
14	Guerra E, Trerotola M, Aloisi AL, et al: The Trop-2 signalling network in cancer growth. Oncogene. 32:1594–1600. 2013. View Article : Google Scholar
15	Cubas R, Li M, Chen C and Yao Q: Trop2: a possible therapeutic target for late stage epithelial carcinomas. Biochim Biophys Acta. 1796:309–314. 2009.PubMed/NCBI
16	Trerotola M, Cantanelli P, Guerra E, et al: Upregulation of Trop-2 quantitatively stimulates human cancer growth. Oncogene. 32:222–233. 2013. View Article : Google Scholar
17	Nishi K, Inoue H, Schnier JB and Rice RH: Cyclin D1 downregulation is important for permanent cell cycle exit and initiation of differentiation induced by anchorage-deprivation in human keratinocytes. J Cell Biochem. 106:63–72. 2009. View Article : Google Scholar
18	Gardner LB, Li Q, Park MS, Flanagan WM, Semenza GL and Dang CV: Hypoxia inhibits G1/S transition through regulation of p27 expression. J Biol Chem. 276:7919–7926. 2001. View Article : Google Scholar
19	Kolch W: Meaningful relationships: the regulation of the Ras/Raf/MEK/ERK pathway by protein interactions. Biochem J. 351:289–305. 2000. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Trop2 inhibition suppresses the proliferation and invasion of laryngeal carcinoma cells via the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway

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