Department of Medical Oncology, Central Hospital, Zhumadian City 463000, China.
Office of Huanghuai University, Zhumadian City 463000, China.
Biosci Rep. 2020 Jun 26;40(6). doi: 10.1042/BSR20193181.
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.
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。
