高表达膜联蛋白 A9 通过 TGF-β 信号通路促进胃癌细胞增殖和迁移。
High Expression of Annexin A9 Promotes Cell Proliferation and Migration in Gastric Cancer via the TGF-β Signaling Pathway.
机构信息
Department of Gastroenterology, Institute of Digestive Diseases, The Affiliated People's Hospital, Jiangsu University, Zhenjiang 212002, Jiangsu, China.
出版信息
J Environ Pathol Toxicol Oncol. 2021;40(3):87-94. doi: 10.1615/JEnvironPatholToxicolOncol.2021038527.
Annexin A9 (ANXA9) represents an important calcium-dependent phospholipid-binding protein family member and contains a calcium-binding site that is necessary for extracellular matrix proteins. ANXA9 has a significant role in human cancers. However, there is no correlation study existing on ANXA9 in gastric cancer (GC). ANXA9 messenger RNA (mRNA) expression within patients with GC were detected with reverse transcription polymerase chain reaction and its protein expression in GC and GES-1 cells were detected through Western blotting. ANXA9 levels within normal and GC tissue samples were measured by Kaplan-Meier analysis and Oncomine. Transwell migration, colony formation, and cell cycle assay monitored the effects of ANXA9 on cell proliferation and metastasis and growth. Additionally, proteins related to epithelial-mesenchymal transition (EMT) were detected to evaluate the function of ANXA9 within GC cells. Relative to GES-1 cells, ANXA9 expression increased within GC cells. Also, ANXA9 expression increased in GC tissues and indicated an unfavorable prognosis. Furthermore, ANXA9 over-expression within HGC-27 cells increased migrated cells quantity and formed larger and more numerous cell clones; the G1 phase decreased while S and G2 phases increased; whereas ANXA9 knockdown suppressed MGC-803 cell growth and migration. Thus, ANXA9 may influence cell growth, migration and EMT through transforming growth factor β (TGF-β) signal transduction pathway. Immunofluorescence analyzed SMAD2/3 and p-SMAD2/3 distribution and expression when ANXA9 was overexpressed in HGC-27 cells. These results predicted that ANXA9 mediated cell migration and growth through TGF-β signal transduction pathway within GC.
膜联蛋白 A9（ANXA9）是一种重要的钙依赖性磷脂结合蛋白家族成员，包含一个钙结合位点，对于细胞外基质蛋白是必需的。ANXA9 在人类癌症中具有重要作用。然而，目前尚没有关于胃癌（GC）中 ANXA9 的相关性研究。通过逆转录聚合酶链反应检测 GC 患者中 ANXA9 的信使 RNA（mRNA）表达，通过 Western blot 检测 ANXA9 在 GC 和 GES-1 细胞中的蛋白表达。通过 Kaplan-Meier 分析和 Oncomine 检测正常和 GC 组织样本中的 ANXA9 水平。Transwell 迁移、集落形成和细胞周期检测监测 ANXA9 对细胞增殖和转移以及生长的影响。此外，还检测了与上皮-间充质转化（EMT）相关的蛋白，以评估 ANXA9 在 GC 细胞中的功能。与 GES-1 细胞相比，GC 细胞中 ANXA9 的表达增加。此外，GC 组织中 ANXA9 的表达增加，并提示预后不良。进一步的，HGC-27 细胞中 ANXA9 的过表达增加了迁移细胞的数量，并形成了更大、更多的细胞克隆；G1 期减少，而 S 和 G2 期增加；而 ANXA9 的敲低抑制了 MGC-803 细胞的生长和迁移。因此，ANXA9 可能通过转化生长因子β（TGF-β）信号转导通路影响细胞生长、迁移和 EMT。当 ANXA9 在 HGC-27 细胞中过表达时，免疫荧光分析 SMAD2/3 和 p-SMAD2/3 的分布和表达。这些结果预测，ANXA9 通过 TGF-β 信号转导通路介导 GC 中的细胞迁移和生长。
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