title: SDF-1/CXCR4 signaling up-regulates survivin to regulate human sacral chondrosarcoma cell cycle and epithelial-mesenchymal transition via ERK and PI3K/AKT pathway.
abstract: Human sacral chondrosarcoma, the most common one of malignant tumors, has a potent capacity to invade locally and metastasize. Notably, CXCR4 and survivin are widely recommended as a candidate of the molecule-targeted therapy. However, the roles and associations of CXCR4 and survivin in sacral chondrosarcoma have not been well characterized. Here, we investigated CXCR4 and survivin expression in human sacral chondrosarcoma. Resected sacral chondrosarcoma specimens were available from 30 patients. In vitro human chondrosarcoma cell lines SW1353 was used. Immunohistochemistry, Western blot, RNA interference, and cell cycle analyses were conducted. Immunohistochemistry revealed that CXCR4 and survivin expressed in 83.3 and 86.7 % of sacral chondrosarcoma tissues, respectively, and both were closely associated with grade and recurrence (p < 0.05). Western blot revealed that survivin expression in SW1353 increased in a dose- and time-dependent manner following SDF-1 treatment. However, the interference with MEK/ERK and PI3K/AKT pathway affected SDF-1-induced up-regulation of survivin. Besides survivin siRNA affected cell cycle progression and the expression of epithelial-mesenchymal transition (EMT) biomarkers: Snail and N-cadherin, when compared with those of non-transfection. In conclusion, the present study shows that SDF-1/CXCR4 signaling up-regulates survivin via MEK/ERK and PI3K/AKT pathway, leading to cell cycle and EMT occurrence in human sacral chondrosarcoma. The antagonizing of CXCR4 and/or survivin might benefit patients with sacral chondrosarcoma.
authors.affiliation: Department of Orthopedics and Traumatology, Nanfang Hospital, Southern Medical University, 1838#, North of Guangzhou Avenue, Guangzhou, 510515, Guangdong, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Yang
authors.forename: Gang
authors.initials: G
authors.lastname: Wang
authors.forename: Hongjun
authors.initials: H
authors.lastname: Huo
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Yuanhang
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000502:physiology; D054377:Chemokine CXCL12 / Q000378:metabolism; D002813:Chondrosarcoma / Q000378:metabolism / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4 / Q000378:metabolism; D012447:Sacrum; D015398:Signal Transduction / Q000502:physiology*; D000077022:Survivin; D015854:Up-Regulation
chemical_list: C107489:BIRC5 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D000077022:Survivin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases