title: Epithelial derived CTGF promotes breast tumor progression via inducing EMT and collagen I fibers deposition.
abstract: Interactions among tumor cells, stromal cells, and extracellular matrix compositions are mediated through cytokines during tumor progression. Our analysis of 132 known cytokines and growth factors in published clinical breast cohorts and our 84 patient-derived xenograft models revealed that the elevated connective tissue growth factor (CTGF) in tumor epithelial cells significantly correlated with poor clinical prognosis and outcomes. CTGF was able to induce tumor cell epithelial-mesenchymal transition (EMT), and promote stroma deposition of collagen I fibers to stimulate tumor growth and metastasis. This process was mediated through CTGF-tumor necrosis factor receptor I (TNFR1)-IκB autocrine signaling. Drug treatments targeting CTGF, TNFR1, and IκB signaling each prohibited the EMT and tumor progression.
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.
authors: Xiaoping
authors: X
authors: Zhu
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.|Department of Radiology, The Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou, China.
authors: Jing
authors: J
authors: Zhong
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.|Department of Radiology, Zhongda Hospital, Nanjing, China.
authors: Zhen
authors: Z
authors: Zhao
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.
authors: Jianting
authors: J
authors: Sheng
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.|Department of Orthopedics, Tongji Hospital, Wuhan, China.
authors: Jiang
authors: J
authors: Wang
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.|Department of Pharmacy, Changhai Hospital, Shanghai, China.
authors: Jiyong
authors: J
authors: Liu
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.
authors: Kemi
authors: K
authors: Cui
authors: Methodist Cancer Center, Houston Methodist Hospital, Houston, TX, USA.
authors: Jenny
authors: J
authors: Chang
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.
authors: Hong
authors: H
authors: Zhao
authors: Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA.|Methodist Cancer Center, Houston Methodist Hospital, Houston, TX, USA.
authors: Stephen
authors: S
authors: Wong
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D019898:Autocrine Communication; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism*; D055513:Connective Tissue Growth Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020672:I-kappa B Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D053208:Kaplan-Meier Estimate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D034622:RNA Interference; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C526317:CCN2 protein, human; D024042:Collagen Type I; D020672:I-kappa B Proteins; D047888:Receptors, Tumor Necrosis Factor, Type I; C506235:TNFRSF1A protein, human; D055513:Connective Tissue Growth Factor
keywords: breast cancer; collagen I fibers; connective tissue growth factor (CTGF); epithelial-mesenchymal transition (EMT); tumor necrosis factor receptor 1 (TNFR1) pathway