Department of General Surgery, The Second Xiangya Hospital of Central South University, Changsha 410001, China.
Department of General Surgery, Clinical Medical College of Yangzhou University, Yangzhou 225001, China.
Acta Biochim Biophys Sin (Shanghai). 2021 May 21;53(6):697-706. doi: 10.1093/abbs/gmab038.
Signal transducing adaptor molecule 2 (STAM2) is a phosphotyrosine protein, which regulates receptor signaling and trafficking of mammalian cells. However, its role in gastric cancer (GC) remains undiscovered. In this study, we aimed to investigate the functions of STAM2 in GC. The mRNA and protein expression levels of STAM2 were measured by quantitative real-time PCR, western blot analysis, and immunohistochemistry. STAM2 was stably silenced in AGS and HGC-27 cells using small interfering RNA. The function of STAM2 in GC cells was further investigated by CCK-8 assay, EdU incorporation assay, flow cytometry, and scratch wound healing and Boyden chamber assays. Additionally, we conducted biological pathway enrichment analysis and rescue assays to explore the effects of STAM2 on JAK/STAT signaling pathway. Our results showed that STAM2 is remarkably highly expressed in GC tissues and cells, and overexpressed STAM2 is correlated with tumor size, advanced tumor node metastasis stage, and poor prognosis. In addition, STAM2 knockdown could significantly inhibit proliferation, block cell cycle, and restrain migration and invasion capabilities of GC cells. Mechanistically, we found that STAM2 knockdown effectively decreased the expressions of MMP2 and MMP9 and the phosphorylation levels of JAK2 and STAT3. Taken together, this study revealed that STAM2 knockdown could suppress malignant process by targeting the JAK2/STAT3 signaling pathway in GC.
信号转导衔接子分子 2（STAM2）是一种磷酸酪氨酸蛋白，调节哺乳动物细胞的受体信号转导和运输。然而，其在胃癌（GC）中的作用尚未被发现。在本研究中，我们旨在研究 STAM2 在 GC 中的功能。通过定量实时 PCR、western blot 分析和免疫组织化学测定 STAM2 的 mRNA 和蛋白表达水平。使用小干扰 RNA 稳定沉默 AGS 和 HGC-27 细胞中的 STAM2。通过 CCK-8 测定、EdU 掺入测定、流式细胞术、划痕愈合和 Boyden 室测定进一步研究 STAM2 在 GC 细胞中的功能。此外，我们进行了生物途径富集分析和挽救实验，以探讨 STAM2 对 JAK/STAT 信号通路的影响。我们的结果表明，STAM2 在 GC 组织和细胞中显著高表达，过表达的 STAM2与肿瘤大小、晚期肿瘤淋巴结转移分期和不良预后相关。此外，STAM2 敲低可显著抑制 GC 细胞的增殖、阻滞细胞周期，并抑制其迁移和侵袭能力。在机制上，我们发现 STAM2 敲低可通过靶向 JAK2/STAT3 信号通路有效降低 MMP2 和 MMP9 的表达以及 JAK2 和 STAT3 的磷酸化水平。总之，这项研究揭示了 STAM2 敲低通过靶向 JAK2/STAT3 信号通路可抑制 GC 的恶性进程。
Zotero 插件