Oncotarget

Research Papers:

Human sulfatase 1 exerts anti-tumor activity by inhibiting the AKT/ CDK4 signaling pathway in melanoma

Xiaoli Lou, Bin Sun, Jianxing Song, Yicun Wang, Junhao Jiang, Yang Xu, Zeqiang Ren and Changqing Su _

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Oncotarget. 2016; 7:84486-84495. https://doi.org/10.18632/oncotarget.12996

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Abstract

Xiaoli Lou1, Bin Sun2, Jianxing Song1, Yicun Wang3, Junhao Jiang4, Yang Xu2, Zeqiang Ren4, Changqing Su2,4

1Department of Reconstructive Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China

2Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200433, China

3Department of Orthopedics, Jinling Hospital, Nanjing University Medical College, Nanjing 210002, China

4Cancer Center for Collaborative Innovation, Affiliated Peixian People’s Hospital of Xuzhou Medical University, Jiangsu Peixian 221600, China

Correspondence to:

Changqing Su, email: suchangqing@gmail.com

Zeqiang Ren, email: rzq0805@189.cn

Keywords: human sulfatase 1 (hSulf-1), protein kinase B (AKT), cyclin-dependent kinase (CDK4), signaling pathway, melanoma

Received: August 24, 2016     Accepted: October 24, 2016     Published: October 31, 2016

ABSTRACT

Human sulfatase 1 (hSulf-1) has aryl sulfatase activity. It can reduce the sulfation of cell surface heparan sulfate proteoglycan (HSPG) and inhibit various growth factor receptor-mediated signaling pathways. In most cancers, hSulf-1 is inactivated, which endows cancer cells with increasesed cell proliferation and metastatic activities, inhibition of apoptosis, and decreased sensitivity to radio- and chemotherapy. In this study, we found that hSulf-1 overexpression in melanoma cells can inhibit cell proliferation and induce cell cycle arrest and apoptosis by decreasing the protein kinase B (AKT) phosphorylation and limiting CDK4 nuclear import. We further confirmed that hSulf-1 overexpression can inhibit AKT phosphorylation and CDK4 nuclear localization and retard the growth of melanoma xenograft tumors in nude mice. Overall, hSulf-1 function in melanoma cells provides an ideal molecular treatment target. An important anti-tumor mechanism of hSulf-1 operates by decreasing downstream AKT signaling pathway activity and inhibiting the nuclear import of CDK4.


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