Role of Sciellin in gallbladder cancer proliferation and formation of neutrophil extracellular traps.
Role of Sciellin in gallbladder cancer proliferation and formation of neutrophil extracellular traps.
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DOI：
10.1038/s41419-020-03286-z
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发表时间：
2021-01-06
影响因子：
9
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Li Y;Yuan R;Ren T;Yang B;Miao H;Liu L;Li Y;Cai C;Yang Y;Hu Y;Jiang C;Xu Q;Zhang Y;Liu Y
除了原发肿瘤的发展和转移，肿瘤相关血栓形成是恶性实体瘤患者癌症死亡的第二大原因。然而，胆囊癌（GBC）和癌症相关血栓形成的机制尚不清楚。本研究旨在探讨scellin （SCEL）在GBC细胞增殖和静脉血栓栓塞发生中的机制作用。免疫组织化学染色法检测SCEL的表达水平。采用分子生物学和细胞生物学方法研究了SCEL在胆囊癌细胞中的作用。SCEL在GBC中明显上调，并与TNM晚期和不良预后相关。此外，SCEL与EGFR相互作用，稳定EGFR表达，激活下游PI3K和Akt通路，导致细胞增殖。此外，SCEL诱导肿瘤细胞产生IL-8，刺激中性粒细胞胞外陷阱（NETs）的形成，加速血栓栓塞。在异种移植物中，与对照细胞相比，表达scel的GBCs发生了更大的肿瘤和血栓形成。目前的研究结果表明，SCEL促进GBC细胞增殖并诱导net相关血栓形成，因此可以作为潜在的治疗靶点。
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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影响因子：
4.8
作者：
Champliaud, MF;Burgeson, RE;Olson, PF
通讯作者：
Olson, PF
影响因子：
11.2
作者：
Cedervall, Jessica;Zhang, Yanyu;Olsson, Anna-Karin
通讯作者：
Olsson, Anna-Karin
DOI：
10.1074/jbc.m114.575464
发表时间：
2014-07-25
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Makinoshima H;Takita M;Matsumoto S;Yagishita A;Owada S;Esumi H;Tsuchihara K
通讯作者：
Tsuchihara K
影响因子：
4.6
作者：
Leal AC;Mizurini DM;Gomes T;Rochael NC;Saraiva EM;Dias MS;Werneck CC;Sielski MS;Vicente CP;Monteiro RQ
通讯作者：
Monteiro RQ
胆囊癌中 miR-143-3p 靶向 ITGA6 通过 PI3K/AKT 通路下调 PLGF 表达来抑制肿瘤生长和血管生成
影响因子：
9
作者：
Jin YP;Hu YP;Wu XS;Wu YS;Ye YY;Li HF;Liu YC;Jiang L;Liu FT;Zhang YJ;Hao YJ;Liu XY;Liu YB
通讯作者：
Liu YB