title: CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib.
abstract: Gastrointestinal stromal tumor (GIST) is the most major mesenchymal neoplasm of the digestive tract. Up to now, imatinib mesylate has been used as a standard first-line treatment for irresectable and metastasized GIST patients or adjuvant treatment for advanced GIST patients who received surgical resection. However, secondary resistance to imatinib usually happens, resulting in a major obstacle in GIST successful therapy. In this study, we first found that collagen and calcium binding EGF domains 1 (CCBE1) expression gradually elevated along with the risk degree of NIH classification, and poor prognosis emerged in the CCBE1-positive patients. In vitro experiments showed that recombinant CCBE1 protein can enhance angiogenesis and neutralize partial effect of imatinib on the GIST-T1 cells. In conclusion, these data indicated that CCBE1 may be served as a new predictor of prognosis in post-operative GIST patients and may play an important role in stimulating GIST progression.
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.|Shanghai Medical College of Fudan University, Shanghai, 200032, P.R. China.
authors: Guang-Ang
authors: GA
authors: Tian
authors: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
authors: Chun-Chao
authors: CC
authors: Zhu
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
authors: Xiao-Xin
authors: XX
authors: Zhang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
authors: Lei
authors: L
authors: Zhu
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
authors: Xiao-Mei
authors: XM
authors: Yang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.|Shanghai Medical College of Fudan University, Shanghai, 200032, P.R. China.
authors: Shu-Heng
authors: SH
authors: Jiang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
authors: Rong-Kun
authors: RK
authors: Li
authors: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
authors: Lin
authors: L
authors: Tu
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.|Shanghai Medical College of Fudan University, Shanghai, 200032, P.R. China.
authors: Yang
authors: Y
authors: Wang
authors: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
authors: Chun
authors: C
authors: Zhuang
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
authors: Ping
authors: P
authors: He
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.|Shanghai Medical College of Fudan University, Shanghai, 200032, P.R. China.
authors: Qing
authors: Q
authors: Li
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
authors: Xiao-Yan
authors: XY
authors: Cao
authors: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, P.R. China.
authors: Hui
authors: H
authors: Cao
authors: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, P.R. China.
authors: Zhi-Gang
authors: ZG
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D004351:Drug Resistance; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy / Q000378:metabolism* / Q000401:mortality; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D011379:Prognosis; D016019:Survival Analysis; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C546964:CCBE1 protein, human; D002135:Calcium-Binding Proteins; D025521:Tumor Suppressor Proteins; D000068877:Imatinib Mesylate