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Deprecated: Implicit conversion from float 251.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Oncotarget 2016 ; 7 (51): 84486-95 Nephropedia Template TP
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Human sulfatase 1 exerts anti-tumor activity by inhibiting the AKT/ CDK4 signaling pathway in melanoma #MMPMID27806323
Lou X; Sun B; Song J; Wang Y; Jiang J; Xu Y; Ren Z; Su C
Oncotarget 2016[Dec]; 7 (51): 84486-95 PMID27806323show ga
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.