title: Up-regulation of syncytin-1 contributes to TNF-α-enhanced fusion between OSCC and HUVECs partly via Wnt/β-catenin-dependent pathway.
abstract: Accumulating evidence implies that cell fusion is one of the driving forces of cancer invasion and metastasis. However, considerably less is still known about the triggering factors and underlying mechanisms associated with cancer-host cell fusion, particularly in inflammatory tumor microenvironment. In this study, we confirmed that inflammatory factor TNF-α could enhance fusion between squamous cell carcinoma cells 9 (SCC-9) and human umbilical vein endothelial cells (HUVEC). Further study revealed that TNF-α could promote up-regulation of syncytin-1 in SCC-9 and its receptor neutral amino acid transporter type 2 (ASCT-2) in HUVEC. Syncytin-1 acted as an important downstream effector in TNF-α-enhanced cancer-endothelial cell fusion. TNF-α treatment also led to the activation of Wnt/β-catenin signal pathway in SCC-9. The activation of Wnt/β-catenin signal pathway was closely associated with the up-regulation of syncytin-1 in SCC-9 and increased fusion between SCC-9 and HUVEC while blocking of Wnt/β-catenin signal pathway resulted in the corresponding down-regulation of syncytin-1 accompanied by sharp decrease of cancer-endothelial cell fusion. Taking together, our results suggest that Wnt/β-catenin signal pathway activation-dependent up-regulation of syncytin-1 contributes to the pro-inflammatory factor TNF-α-enhanced fusion between oral squamous cell carcinoma cells and endothelial cells.
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Ting-Lin
authors.initials: TL
authors.lastname: Yan
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Huang
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Xiao-Cheng
authors.initials: XC
authors.lastname: Zhou
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.
authors.forename: Er-Hui
authors.initials: EH
authors.lastname: Jiang
authors.affiliation: Center of Stomatology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhao
authors.affiliation: Department of Stomatology, Liuzhou People's Hospital, Guangxi, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Oral and Maxillofacial Surgery, The Affliated Hospital of Qingdao University, Qingdao, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Song
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oromaxillofacial &Head NeckOncology, School &Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Shao
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oromaxillofacial &Head NeckOncology, School &Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Liu
authors.affiliation: The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) &Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan, China.|Department of Oromaxillofacial &Head NeckOncology, School &Hospital of Stomatology, Wuhan University, Wuhan, China.
authors.forename: Zheng-Jun
authors.initials: ZJ
authors.lastname: Shang
mesh_terms: D026962:Amino Acid Transport System ASC / Q000378:metabolism; D002459:Cell Fusion; D002460:Cell Line; D042783:Endothelial Cells / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D015686:Gene Products, env / Q000378:metabolism*; D006801:Humans; D015778:Minor Histocompatibility Antigens / Q000378:metabolism; D011257:Pregnancy Proteins / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D015854:Up-Regulation; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D026962:Amino Acid Transport System ASC; D015686:Gene Products, env; D015778:Minor Histocompatibility Antigens; D011257:Pregnancy Proteins; C420506:SLC1A5 protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D051176:beta Catenin; C405335:syncytin