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Hedgehog 信号激活对于糖蛋白 6 介导的胃癌细胞侵袭、迁移和上皮间质转化的调节是必需的。

Hedgehog signaling activation required for glypican-6-mediated regulation of invasion, migration, and epithelial-mesenchymal transition of gastric cancer cells.

机构信息

Department of Medical Oncology, Central Hospital, Zhumadian City 463000, China.

Office of Huanghuai University, Zhumadian City 463000, China.

出版信息

Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20193181.

Abstract

Gastric cancer (GC) is the fifth most common cancer worldwide and one of the most aggressive cancers in China. Glypican 6 is highly expressed in gastric adenocarcinoma and may act as a diagnostic and prognostic marker; however, the functional importance and molecular mechanism of glypican 6 in GC remains unclear. In the current study, we aimed to reveal the function and mechanism of glypican 6 in two GC cell lines: MKN-45 and SGC-7901. We found higher expression of glypican 6 in MKN-45 and SGC-7901 cells than in cells from the normal gastric mucosa epithelial cell line GES-1. Glypican 6 knockdown suppressed MKN-45 and SGC-7901 cell proliferation. A Transwell assay confirmed that glypican 6 silencing inhibited the migration and invasiveness of MKN-45 and SGC-7901 cells. Epithelial-to-mesenchymal transition (EMT) markers were determined by western blotting, and the results showed reduced Vimentin expression and elevated E-cadherin expression in glypican 6 short interfering RNA (siRNA) transfected MKN-45 and SGC-7901 cells. However, glypican 6 overexpression in GES-1 cells showed no significant promotion on GES-1 cells proliferation and migration. Further studies confirmed that glypican 6 siRNA regulated Hedgehog and Gli1 signaling and participated in the function of glypican 6 on MKN-45 and SGC-7901 cell migration and invasion. Our findings suggest that decreased glypican 6 expression inhibits the migration and invasion ability of GC cells.

摘要

胃癌(GC)是全球第五大常见癌症,也是中国最具侵袭性的癌症之一。Glypican 6 在胃腺癌中高度表达,可能作为诊断和预后标志物;然而,Glypican 6 在 GC 中的功能重要性和分子机制尚不清楚。在本研究中,我们旨在揭示 Glypican 6 在两种 GC 细胞系(MKN-45 和 SGC-7901)中的功能和机制。我们发现 Glypican 6 在 MKN-45 和 SGC-7901 细胞中的表达高于正常胃黏膜上皮细胞系 GES-1 中的细胞。Glypican 6 敲低抑制了 MKN-45 和 SGC-7901 细胞的增殖。Transwell 测定证实,Glypican 6 沉默抑制了 MKN-45 和 SGC-7901 细胞的迁移和侵袭。通过 Western blot 测定上皮间质转化(EMT)标志物,结果表明 Glypican 6 siRNA 转染的 MKN-45 和 SGC-7901 细胞中 Vimentin 表达减少,E-cadherin 表达增加。然而,Glypican 6 在 GES-1 细胞中的过表达对 GES-1 细胞的增殖和迁移没有明显促进作用。进一步的研究证实,Glypican 6 siRNA 调节 Hedgehog 和 Gli1 信号通路,并参与 Glypican 6 对 MKN-45 和 SGC-7901 细胞迁移和侵袭功能的调节。我们的研究结果表明,降低 Glypican 6 的表达抑制了 GC 细胞的迁移和侵袭能力。

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