Glypican 1 promotes proliferation and migration in esophagogastric adenocarcinoma via activating AKT/GSK/β-catenin pathway

Abstract

Background: Glypican 1 (GPC1) is a heparan sulphate proteoglycan cell membrane protein. It is implicated in driving cancers of the breast, brain, pancreas, and prostate; however, its role in esophagogastric cancer (EGAC) remains unexplored. The aim of the study was to investigate and elucidate the molecular mechanistic of GPC1 in human EGAC.Methods: Thirty tissue and 120 microarray sections of EGAC were evaluated with Anti-GPC1 immunohistochemistry. Loss and gain of GPC1 function were performed using lentivirus transfection in EGAC cell lines. Mechanistically, AKT/GSK/β-catenin pathway was evaluated using AKT inhibitor MK-2206 and Wnt/β-catenin stimulant LiCl.Results: GPC1 overexpression was found in 102 cases (68%). Overexpression of GPC1 correlated with lymph node metastasis, poor differentiation and decreased overall survival. Lentivirus mediated GPC1 knockdown resulted in decreased cell proliferation, migration, invasion, and colony formation. Knockdown caused G0/G1 cell cycle arrest, increased apoptosis, and reduced EMT. GPC1 mediated its effects by activation of AKT/GSK/β-catenin pathway.Conclusions: This is the first descriptive study to decipher the role of GPC1 in EGAC. Our results suggest that GPC1 regulates cell proliferation and growth and may serve as an attractive oncotarget in EGAC.

Value of Glypican-1 Expression in Pleural Epithelioid Mesothelioma, Adenocarcinoma and Squamous Cell Carcinoma of the Lung

“…We observed that GPC1 expression was upregulated in association with the presence of nodal metastasis. This was in accordance with previous studies reporting that GPC1 plays a role in controlling cell migration [22]. In addition, GPC1 plays a key role in cancer progression and metastasis; GPC1 down-regulation has been noted to inhibit metastasis in pancreatic cancer cell lines [20].…”

Targeting Glypican-1 Reverses Resistance to 5-Fluorouracil in Esophageal Adenocarcinoma Cells

“…Transfection and establishment of stable cell line. Short hairpin RNA (shRNA) targeting GPC-1 was designed using a previously published protocol (7). The control scramble shRNA (SCR) was used as a negative control.…”

“…Therefore, the current scenario necessitates the prompt exploration of novel therapeutic approaches that can effectively address the challenges of multidrug resistance in EAC. In a recent study, our group identified the critical role of Glypican-1 (GPC-1) in the progression of EAC (7). GPC-1 is a member of the family of glycoproteins known as membrane heparan sulfate proteoglycans (8).…”

Extracellular Vesicular Analysis of Glypican 1 mRNA and Protein for Pancreatic Cancer Diagnosis and Prognosis

“…Their primary role involves regulating the Wnts, Hedgehogs, fibroblast growth factors, and bone morphogenetic protein signaling pathways. [ 16 ] Glypican‐1 (GPC1) expression is notably elevated in various cancer types, including PDAC, [ 15 ] breast cancer, [ 17 ] esophageal squamous cell carcinoma, [ 18 ] glioblastoma, [ 19 ] colorectal cancer, [ 20 ] hepatocellular carcinoma, [ 21 ] and cervical cancer. [ 22 ] Transfecting GPC1 RNAi has demonstrated the ability to impede the mitogenic response in cultured colorectal cancer cells, [ 23 ] establishing GPC1 as a potential biomarker for cancer detection.…”