title: A systems biology approach identifies effective tumor-stroma common targets for oral squamous cell carcinoma.
abstract: The complex interactions between cancer cells and their surrounding stromal microenvironment play important roles in tumor initiation and progression and represent viable targets for therapeutic intervention. Here, we propose a concept of common target perturbation (CTP). CTP acts simultaneously on the same target in both the tumor and its stroma that generates a bilateral disruption for potentially improved cancer therapy. To employ this concept, we designed a systems biology strategy by combining experiment and computation to identify potential common target. Through progressive cycles of identification, TGF-β receptor III (TβRIII) is found as an epithelial-mesenchymal common target in oral squamous cell carcinoma. Simultaneous perturbation of TβRIII in the oral cancerous epithelial cells and their adjacent carcinoma-associated fibroblasts effectively inhibits tumor growth in vivo, and shows superiority to the unilateral perturbation of TβRIII in either cell type alone. This study indicates the strong potential to identify therapeutic targets by considering cancer cells and their adjacent stroma simultaneously. The CTP concept combined with our common target discovery strategy provides a framework for future targeted cancer combinatorial therapies.
authors.affiliation: Authors' Affiliations: State Key Laboratory of Oral Diseases; Department of Oral Medicine, West China Hospital of Stomatology; Departments of Oral Oncology and Oral Pathology, West China School of Stomatology, Sichuan University; The Third People's Hospital of Chengdu, The Second Affiliated Hospital of Chengdu Chongqing Medical University, Chengdu, Sichuan; Guangdong Provincial Stomatological Hospital and the Affiliated Stomatological Hospital of Southern Medical University, Guangzhou, Guangdong; Key Laboratory of Oral Disease Research of Anhui Province, College of Stomatology, Anhui Medical University; and Hefei National Laboratory for Physical Sciences at Microscale and School of Life Science, University of Science and Technology of China, Hefei, Anhui, China.
authors.forename: Wenxia
authors.initials: W
authors.lastname: Meng
authors.forename: Yun
authors.initials: Y
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: He
authors.forename: Chuanxia
authors.initials: C
authors.lastname: Liu
authors.forename: Qinghong
authors.initials: Q
authors.lastname: Gao
authors.forename: Lin
authors.initials: L
authors.lastname: Ge
authors.forename: Lanyan
authors.initials: L
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Yiqing
authors.initials: Y
authors.lastname: Guo
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Li
authors.forename: Yurong
authors.initials: Y
authors.lastname: Liu
authors.forename: Sixiu
authors.initials: S
authors.lastname: Chen
authors.forename: Xiangli
authors.initials: X
authors.lastname: Kong
authors.forename: Zhi
authors.initials: Z
authors.lastname: Liang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005347:Fibroblasts / Q000473:pathology; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D000077195:Squamous Cell Carcinoma of Head and Neck; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology*; D014162:Transfection
chemical_list: D018125:Receptors, Transforming Growth Factor beta