| Literature DB >> 33414368 |
Yang Li1,2,3, Ruiyan Yuan1,2,3, Tai Ren1,2,3, Bo Yang4, Huijie Miao1,2,3, Liguo Liu1,2,3, Yongsheng Li1,2,3, Chen Cai1,2,3, Yang Yang1,2,3, Yunping Hu1,2,3, Chengkai Jiang1,2,3, Qindie Xu5, Yijian Zhang6,7,8, Yingbin Liu9,10.
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.Entities:
Year: 2021 PMID： 33414368 PMCID： PMC7791032 DOI： 10.1038/s41419-020-03286-z
Source DB: PubMed Journal: Cell Death Dis Impact factor: 8.469