SCAMP1 silencing inhibits proliferation by attenuating multiple pro-survival signaling pathways in gastric cancer.

IF 3.3 3区 医学 Q2 ONCOLOGY Journal of Cancer Pub Date : 2024-09-09 eCollection Date: 2024-01-01 DOI:10.7150/jca.99610
Gang Ma, Yang Yang, Fenglin Cai, Bin Ke, Jingyu Deng
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Abstract

Secretory carrier-associated membrane protein 1 (SCAMP1) is the most universally expressed member of the SCAMP family, and its ability to facilitate endocytosis was demonstrated approximately two decades ago. Nevertheless, its roles in cancer biology are largely unknown, although its expression is significantly increased in most cancer types. Herein, we examined the expression of SCAMP1 in gastric cancer (GC) tissues and found that it was aberrantly increased and positively correlated with tumor size and lymph node metastasis. More importantly, increased SCAMP1 expression was associated with poor prognosis in patients with GC. Functional experiments demonstrated that SCAMP1 knockdown markedly suppressed the proliferation of GC cells in vitro and in vivo. RNA sequencing assays demonstrated that SCAMP1 knockdown altered the expression profile of GC cells, and a significant portion of the altered genes were enriched in receptor tyrosine kinases and their related downstream signaling pathways. Immunoblotting confirmed that the Akt/MAPK/Stat signaling pathway was strongly attenuated in GC cells with SCAMP1 depletion. Taken together, these results demonstrated that SCAMP1 drives hyperproliferation in GC cells, thus suggesting that further investigation into the mechanisms and translational value of SCAMP1 in treating patients with GC is warranted.

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沉默 SCAMP1 可通过削弱多种促生存信号通路抑制胃癌的增殖。
分泌载体相关膜蛋白 1(SCAMP1)是 SCAMP 家族中表达最普遍的成员,其促进内吞的能力在大约二十年前就已得到证实。然而,尽管它在大多数癌症类型中的表达量都显著增加,但它在癌症生物学中的作用在很大程度上还不为人所知。在此,我们研究了 SCAMP1 在胃癌(GC)组织中的表达,发现其异常增高并与肿瘤大小和淋巴结转移呈正相关。更重要的是,SCAMP1 表达的增加与胃癌患者的不良预后有关。功能实验证明,敲除 SCAMP1 能显著抑制 GC 细胞在体外和体内的增殖。RNA 测序实验表明,SCAMP1 基因敲除改变了 GC 细胞的表达谱,改变的基因中有相当一部分富含受体酪氨酸激酶及其相关下游信号通路。免疫印迹证实,在去除了 SCAMP1 的 GC 细胞中,Akt/MAPK/Stat 信号通路被强烈削弱。综上所述,这些结果表明,SCAMP1 驱动了 GC 细胞的过度增殖,从而表明有必要进一步研究 SCAMP1 治疗 GC 患者的机制和转化价值。
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来源期刊
Journal of Cancer
Journal of Cancer ONCOLOGY-
CiteScore
8.10
自引率
2.60%
发文量
333
审稿时长
12 weeks
期刊介绍: Journal of Cancer is an open access, peer-reviewed journal with broad scope covering all areas of cancer research, especially novel concepts, new methods, new regimens, new therapeutic agents, and alternative approaches for early detection and intervention of cancer. The Journal is supported by an international editorial board consisting of a distinguished team of cancer researchers. Journal of Cancer aims at rapid publication of high quality results in cancer research while maintaining rigorous peer-review process.
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