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

Chen Zeng,Sen Xiang,Fuli Zhao,Ran Yan,Guanghua Yang

doi:10.1042/bsr20193181

Chen Zeng, Sen Xiang + Show 3 more

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https://doi.org/10.1042/bsr20193181

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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.

Highlights

Gastric cancer (GC), one of the most common cancers, is the third-most lethal cancer in the world after liver and lung cancers [1,2]
Glypican 6 was highly expressed in gastric cancer cells
Consistent with RT-qPCR results, glypican 6 protein levels by western blot analyses were much higher in MKN-45 cells (P = 0.026) and SGC-7901 cells (P = 0.04) than in GES-1 cells (Figure 1B)

Summary

Introduction

Gastric cancer (GC), one of the most common cancers, is the third-most lethal cancer in the world after liver and lung cancers [1,2]. 990000 new cases of GC are diagnosed worldwide, and approximately 738000 patients die from this disease annually [3]. The incidence of GC has declined recently, it remains the fourth-most common malignancy in the world [2]. Despite recent advances in diagnosis, the diagnosis of GC remains a challenge, and most patients are not diagnosed until late stages of the disease [5]. Chemotherapy, surgery, or a combination of therapies can improve patient survival rates, but the median survival time is approximately 12 months for patients with advanced GC [6,7,8]. It is meaningful to identify effective targets and related mechanisms to develop useful therapeutic strategies for GC [9,10]

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