S100A7 Promotes the Migration, Invasion and Metastasis of Human Cervical Cancer Cells Through Epithelial-mesenchymal Transition

Overview

Journal Oncotarget

Specialty Oncology

Date 2017 Feb 18

PMID 28212564

Citations 29

Authors

Tian Tian

Xukun Li

Zhen Hua

Jianlin Ma

Xiaowei Wu

Zhihua Liu

Hongyan Chen

Zhumei Cui

Affiliations

Soon will be listed here.

Abstract

S100A7 is an EF-hand calcium-binding protein that has been suggested to be implicated in cell proliferation, migration, invasion and tumor metastasis. However, its role in cervical cancer has not yet been fully clarified. The present study used immunohistochemistry analysis of S100A7 in clinical specimens of cervical cancer to show that S100A7 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and S100A7 expression in high grade cervical intraepithelial neoplasm (CIN) was significantly higher than cervical cancer. Statistical analysis showed that S100A7 expression was associated with tumor grade (P <0.01) and lymph node metastasis (P <0.05). Functional studies showed that overexpression of S100A7 in cervical cancer cells promoted migration, invasion and metastasis of cervical cancer cells without influencing cell proliferation. Furthermore, S100A7 was found to be secreted into the conditioned media and extracellular S100A7 enhanced cell migration and invasion. Mechanistically, S100A7 bound to RAGE and activated ERK signaling pathway. And S100A7 enhanced cell mesenchymal properties and induced epithelial-mesenchymal transition. In summary, these data reveal a crucial role for S100A7 in regulating cell migration, invasion, metastasis and EMT of cervical cancer and suggest that targeting S100A7 may offer a new targeted strategy for cervical cancer.

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References

Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M . Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014; 136(5):E359-86. DOI: 10.1002/ijc.29210. View

Kwak T, Drews-Elger K, Ergonul A, Miller P, Braley A, Hwang G . Targeting of RAGE-ligand signaling impairs breast cancer cell invasion and metastasis. Oncogene. 2016; 36(11):1559-1572. DOI: 10.1038/onc.2016.324. View

Kaur J, Matta A, Kak I, Srivastava G, Assi J, Leong I . S100A7 overexpression is a predictive marker for high risk of malignant transformation in oral dysplasia. Int J Cancer. 2013; 134(6):1379-88. DOI: 10.1002/ijc.28473. View

Lo J, Yu C, Chiou S, Huang C, Jan C, Lin S . The epithelial-mesenchymal transition mediator S100A4 maintains cancer-initiating cells in head and neck cancers. Cancer Res. 2010; 71(5):1912-23. DOI: 10.1158/0008-5472.CAN-10-2350. View

Mandal S, Curtis L, Pind M, Murphy L, Watson P . S100A7 (psoriasin) influences immune response genes in human breast cancer. Exp Cell Res. 2007; 313(14):3016-25. DOI: 10.1016/j.yexcr.2007.03.020. View

Erhart W, Alkasi O, Brunke G, Wegener F, Maass N, Arnold N . Induction of human β-defensins and psoriasin in vulvovaginal human papillomavirus-associated lesions. J Infect Dis. 2011; 204(3):391-9. DOI: 10.1093/infdis/jir079. View

Deol Y, Nasser M, Yu L, Zou X, Ganju R . Tumor-suppressive effects of psoriasin (S100A7) are mediated through the β-catenin/T cell factor 4 protein pathway in estrogen receptor-positive breast cancer cells. J Biol Chem. 2011; 286(52):44845-54. PMC: 3248020. DOI: 10.1074/jbc.M111.225466. View

Emberley E, Niu Y, Curtis L, Troup S, Mandal S, Myers J . The S100A7-c-Jun activation domain binding protein 1 pathway enhances prosurvival pathways in breast cancer. Cancer Res. 2005; 65(13):5696-702. DOI: 10.1158/0008-5472.CAN-04-3927. View

Liu G, Wu Q, Liu G, Song X, Zhang J . Knockdown of S100A7 reduces lung squamous cell carcinoma cell growth in vitro and in vivo. Int J Clin Exp Pathol. 2015; 7(11):8279-89. PMC: 4270552. View

10.

Chen X, Liu X, Lang H, Zhang S, Luo Y, Zhang J . S100 calcium-binding protein A6 promotes epithelial-mesenchymal transition through β-catenin in pancreatic cancer cell line. PLoS One. 2015; 10(3):e0121319. PMC: 4370615. DOI: 10.1371/journal.pone.0121319. View

11.

Kalluri R, Weinberg R . The basics of epithelial-mesenchymal transition. J Clin Invest. 2009; 119(6):1420-8. PMC: 2689101. DOI: 10.1172/JCI39104. View

12.

Ye L, Sun P, Martin T, Sanders A, Mason M, Jiang W . Psoriasin (S100A7) is a positive regulator of survival and invasion of prostate cancer cells. Urol Oncol. 2012; 31(8):1576-83. DOI: 10.1016/j.urolonc.2012.05.006. View

13.

Tripathi S, Matta A, Kaur J, Grigull J, Chauhan S, Thakar A . Nuclear S100A7 is associated with poor prognosis in head and neck cancer. PLoS One. 2010; 5(8):e11939. PMC: 2914786. DOI: 10.1371/journal.pone.0011939. View

14.

West N, Watson P . S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer. Oncogene. 2010; 29(14):2083-92. DOI: 10.1038/onc.2009.488. View

15.

Kataoka K, Ono T, Murata H, Morishita M, Yamamoto K, Sakaguchi M . S100A7 promotes the migration and invasion of osteosarcoma cells via the receptor for advanced glycation end products. Oncol Lett. 2012; 3(5):1149-1153. PMC: 3389638. DOI: 10.3892/ol.2012.612. View

16.

Hu M, Ye L, Ruge F, Zhi X, Zhang L, Jiang W . The clinical significance of Psoriasin for non-small cell lung cancer patients and its biological impact on lung cancer cell functions. BMC Cancer. 2012; 12:588. PMC: 3537740. DOI: 10.1186/1471-2407-12-588. View

17.

Madsen P, Rasmussen H, Leffers H, Honore B, Dejgaard K, Olsen E . Molecular cloning, occurrence, and expression of a novel partially secreted protein "psoriasin" that is highly up-regulated in psoriatic skin. J Invest Dermatol. 1991; 97(4):701-12. DOI: 10.1111/1523-1747.ep12484041. View

18.

Qi Z, Li T, Kong F, Li Y, Wang R, Wang J . The Characteristics and Function of S100A7 Induction in Squamous Cell Carcinoma: Heterogeneity, Promotion of Cell Proliferation and Suppression of Differentiation. PLoS One. 2015; 10(6):e0128887. PMC: 4460013. DOI: 10.1371/journal.pone.0128887. View

19.

Yin C, Li H, Zhang B, Liu Y, Lu G, Lu S . RAGE-binding S100A8/A9 promotes the migration and invasion of human breast cancer cells through actin polymerization and epithelial-mesenchymal transition. Breast Cancer Res Treat. 2013; 142(2):297-309. DOI: 10.1007/s10549-013-2737-1. View

20.

Gagnon A, Kim J, Schorge J, Ye B, Liu B, Hasselblatt K . Use of a combination of approaches to identify and validate relevant tumor-associated antigens and their corresponding autoantibodies in ovarian cancer patients. Clin Cancer Res. 2008; 14(3):764-71. DOI: 10.1158/1078-0432.CCR-07-0856. View