Epithelial derived CTGF promotes breast tumor progression via inducing EMT and collagen I fibers deposition
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Xiaoping Zhu1,*, Jing Zhong1,2,*, Zhen Zhao1,3, Jianting Sheng1, Jiang Wang1,4, Jiyong Liu1,5, Kemi Cui1, Jenny Chang6, Hong Zhao1, Stephen Wong1,6
1Department of Systems Medicine and Bioengineering, Houston Methodist Research Institute, Weill Cornell Medical College, Houston, TX, USA
2Department of Radiology, The Teaching Hospital of Fujian Medical University, Fujian Provincial Cancer Hospital, Fuzhou, China
3Department of Radiology, Zhongda Hospital, Nanjing, China
4Department of Orthopedics, Tongji Hospital, Wuhan, China
5Department of Pharmacy, Changhai Hospital, Shanghai, China
6Methodist Cancer Center, Houston Methodist Hospital, Houston, TX, USA
*These authors have contributed equally to this work
Hong Zhao, e-mail: [email protected]
Keywords: connective tissue growth factor (CTGF), epithelial-mesenchymal transition (EMT), collagen I fibers, tumor necrosis factor receptor 1 (TNFR1) pathway, breast cancer
Received: April 02, 2015 Accepted: July 17, 2015 Published: July 29, 2015
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.
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