title: Slug signaling is up-regulated by CCL21/CCR7 [corrected] to induce EMT in human chondrosarcoma.
abstract: In recent decades, the CXC chemokine receptor 7 (CCR7) [corrected] and its ligand CCL21 have been extensively reported to be associated with tumorigenesis. Meanwhile, Slug signaling induces the epithelial-mesenchymal transition (EMT) process in chondrosarcoma development. In the present study, we explored the functions of CCL21/CCR7 [corrected] in Slug-mediated EMT in the chondrosarcoma. We analyzed protein expression of CCR7 [corrected] and Slug in human chondrosarcoma samples. Effects of CCR7 [corrected] on chondrosarcoma cells were assessed by in vitro assays. Additionally, CCR7 [corrected] pathways were further investigated by pharmacological and genetic approaches. We found that the altered CCR7 [corrected] (81.7 %) and Slug (85.0 %) expression in human chondrosarcoma tissues were significantly associated with grade, recurrence, and 5-year overall survival. According to in vitro assays, CCL21 stimulation induced the expression of phosph-ERK, phosph-AKT, Slug and N-cadherin in SW1353 cells, while the expression of E-cadherin was down-regulated. Furthermore, Slug signaling modulated E- to N-cadherin switch, which was influenced by the kinase inhibitor PD98059 and LY294002. In addition, the genetic silencing of Slug inhibited the capacity of migration and invasion of SW1353 cells. In conclusion, CCL21/CCR7 [corrected] pathway activates ERK and PI3K/AKT signallings to up-regulate Slug pathway, leading to the occurrence of EMT process in human chondrosarcoma. This study lays a new foundation for molecule-targeted therapy of human chondrosarcoma.
authors.affiliation: Department of Orthopedics, Longgang Orthopedics Hospital of Shenzhen, 243# Yangmeigang, Longgang Street, Longgang District, Shenzhen, 518116, Guangdong, China.
authors.forename: Guosong
authors.initials: G
authors.lastname: Li
authors.forename: Yanjun
authors.initials: Y
authors.lastname: Yang
authors.forename: Siliang
authors.initials: S
authors.lastname: Xu
authors.forename: Lifeng
authors.initials: L
authors.lastname: Ma
authors.forename: Mingtang
authors.initials: M
authors.lastname: He
authors.forename: Ziqing
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000328:Adult; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D045744:Cell Line, Tumor; D054421:Chemokine CCL21 / Q000378:metabolism*; D002813:Chondrosarcoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D034741:RNA, Small Interfering; D054387:Receptors, CXCR / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation
chemical_list: C501896:ACKR3 protein, human; C515478:CCL21 protein, human; D054421:Chemokine CCL21; D034741:RNA, Small Interfering; D054387:Receptors, CXCR; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors