Human sulfatase 1 exerts anti-tumor activity by inhibiting the AKT/ CDK4 signaling pathway in melanoma.
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.
Department of Reconstructive Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Xiaoli
X
Lou
Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200433, China.
Bin
B
Sun
Department of Reconstructive Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Jianxing
J
Song
Department of Orthopedics, Jinling Hospital, Nanjing University Medical College, Nanjing 210002, China.
Yicun
Y
Wang
Cancer Center for Collaborative Innovation, Affiliated Peixian People's Hospital of Xuzhou Medical University, Jiangsu Peixian 221600, China.
Junhao
J
Jiang
Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200433, China.
Yang
Y
Xu
Cancer Center for Collaborative Innovation, Affiliated Peixian People's Hospital of Xuzhou Medical University, Jiangsu Peixian 221600, China.
Zeqiang
Z
Ren
Department of Molecular Oncology, Eastern Hepatobiliary Surgery Hospital and National Center of Liver Cancer, Second Military Medical University, Shanghai 200433, China.|Cancer Center for Collaborative Innovation, Affiliated Peixian People's Hospital of Xuzhou Medical University, Jiangsu Peixian 221600, China.
Changqing
C
Su
D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000235:genetics*; D015238:Sulfotransferases / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous
D051057:Proto-Oncogene Proteins c-akt; D051358:Cyclin-Dependent Kinase 4; C470791:SULF1 protein, human; D015238:Sulfotransferases
cyclin-dependent kinase (CDK4); human sulfatase 1 (hSulf-1); melanoma; protein kinase B (AKT); signaling pathway