Abstract
As a cell surface proteoglycan anchored by glycosyl-phosphatidylinositol, Glypican-3 (GPC3) is reported to be highly expressed in hepatocellular carcinoma (HCC) and to promote cell proliferation and tumorigenesis through activating Wnt/β-catenin signalling. GPC3 is also overexpressed in lung squamous cell carcinoma (SCC), but its effects and mechanisms in the progression of lung SCC remain unknown. The present study aims to explore the role and molecular mechanism of GPC3 in the occurrence and development of lung SCC. Immunohistochemistry, Western blot (WB) and real-time PCR (RT-PCR) assays were used to determine the expression patterns of GPC3 in lung SCC tissues and cells. MTT, flow cytometry and in vivo xenotransplantation assays were used to evaluate the influence of GPC3 on the growth, apoptosis and tumorigenesis of lung SCC cells. The results showed that GPC3 expression levels in lung SCC tissues and cells were significantly elevated, and the high expression of GPC3 significantly promoted cell growth and tumorigenesis and repressed cell apoptosis, as well as increased β-catenin expression. Moreover, knockdown of β-catenin obviously weakened GPC3 role in the promotion of cell proliferation and tumorigenesis, as well as the inhibition of cell apoptosis. In conclusion, the present study demonstrates that up-regulation of GPC3 accelerates the progression of lung SCC in a β-catenin-dependent manner. Our study provides a theoretical basis for GPC3/β-catenin as a novel diagnostic marker and therapeutic target for lung SCC.
Highlights
Lung cancer is one of the most frequently diagnosed malignancies and is the leading cause of cancer-related deaths in the world [1]
The results demonstrated that GPC3 expression at both the protein and mRNA levels was elevated in lung squamous cell carcinoma (SCC) tissues compared with adjacent non-tumour tissues (Figure 1A–C)
We tested the expression of GPC3 in the normal lung cell line BEAS-2B and lung SCC cell lines including LTEP-s, NCI-H520, NCI-H226 and SK-MES-1
Summary
Lung cancer is one of the most frequently diagnosed malignancies and is the leading cause of cancer-related deaths in the world [1]. Non-small cell lung cancer (NSCLC) comprises approximately 85% of all types of lung cancer cases, among which lung adenocarcinoma (AC) and lung squamous cell carcinoma (SCC) are the two most common histologic subtypes [2]. SCC accounts for approximately 35% of NSCLC cases and causes an estimated 0.4 million deaths every year worldwide [3]. Glypican-3 (GPC3) is a cell surface proteoglycan anchored by glycosyl-phosphatidylinositol, which was first discovered in patients with Simpson–Golabi–Behmel syndrome [8]. GPC3 serves as a membrane co-receptor for heparin-binding growth factors, including Hedgehog (Hh) proteins, Wnts and fibroblast growth factors, thereby modulating cell growth, apoptosis and differentiation [9,10]. It was recently reported that GPC3 was overexpressed in the serum samples of hepatocellular carcinoma (HCC)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
