Ma Gang, Yang Yang, Cai Fenglin, Ke Bin, Deng Jingyu
Department of Gastric Surgery, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Tianjin Key Laboratory of Digestive Cancer, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China.
Department of Anesthesiology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer; Tianjin Key Laboratory of Digestive Cancer, Tianjin; Tianjin's Clinical Research Center for Cancer, Tianjin, 300060, P. R. China.
J Cancer. 2024 Sep 9;15(17):5762-5772. doi: 10.7150/jca.99610. eCollection 2024.
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 and . 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.
分泌载体相关膜蛋白1(SCAMP1)是SCAMP家族中表达最为广泛的成员,大约二十年前就已证实其具有促进内吞作用的能力。然而,尽管在大多数癌症类型中其表达显著增加,但其在癌症生物学中的作用仍 largely unknown。在此,我们检测了SCAMP1在胃癌(GC)组织中的表达,发现其异常升高,且与肿瘤大小和淋巴结转移呈正相关。更重要的是,SCAMP1表达增加与GC患者的不良预后相关。功能实验表明,敲低SCAMP1可显著抑制GC细胞的增殖 。RNA测序分析表明,敲低SCAMP1会改变GC细胞的表达谱,且很大一部分改变的基因在受体酪氨酸激酶及其相关下游信号通路中富集。免疫印迹证实,在SCAMP1缺失的GC细胞中,Akt/MAPK/Stat信号通路受到强烈抑制。综上所述,这些结果表明SCAMP1驱动GC细胞过度增殖,因此有必要进一步研究SCAMP1在治疗GC患者中的机制和转化价值。