癌症研究
胆囊癌
细胞生长
癌症
PI3K/AKT/mTOR通路
转移
中性粒细胞胞外陷阱
恶性肿瘤
癌细胞
生物
医学
病理
信号转导
免疫学
内科学
细胞生物学
炎症
遗传学
作者
Li Yang,Ruiyan Yuan,Tianhui Ren,Bo Yang,Huijie Miao,Liguo Liu,Yongsheng Li,Chen Cai,Yang Yang,Yunping Hu,Chengkai Jiang,Qindie Xu,Yijian Zhang,Yingbin Liu
标识
DOI:10.1038/s41419-020-03286-z
摘要
Abstract Apart from primary tumor development and metastasis, cancer-associated thrombosis is the second cause of cancer death in solid tumor malignancy. However, the mechanistic insight into the development of gallbladder cancer (GBC) and cancer-associated thrombosis remains unclear. This study aimed to investigate the mechanistic role of Sciellin (SCEL) in GBC cell proliferation and the development of venous thromboembolism. The expression level of SCEL was determined by immunohistochemical staining. Roles of SCEL in gallbladder cancer cell were determined by molecular and cell biology methods. SCEL was markedly upregulated in GBC and associated with advanced TNM stages and a poor prognosis. Furthermore, SCEL interacted with EGFR and stabilized EGFR expression that activates downstream PI3K and Akt pathway, leading to cell proliferation. In addition, SCEL induces tumor cell IL-8 production that stimulates the formation of neutrophil extracellular traps (NETs), accelerating thromboembolism. In xenografts, SCEL-expressing GBCs developed larger tumors and thrombosis compared with control cells. The present results indicate that SCEL promotes GBC cell proliferation and induces NET-associated thrombosis, thus serving as a potential therapeutic target.
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