Attenuation of cancer proliferation by suppression of glypican-1 and its pleiotropic effects in neoplastic behavior

Sep 24, 2026

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Glypicans (GPC1–6) are linked to tumorigenic processes, and this study performs a cancer-wide GPC expression analysis using The Cancer Genome Atlas patient data. Results show net upregulation of GPC1 and GPC2 in primary solid tumors, while GPC3, GPC5, and GPC6 are downregulated versus normal tissues. High GPC1 expression associates with poor prognosis across multiple cancer types. In vitro CRISPR/Cas9, siRNA, or anti-GPC1 antibody targeting attenuates proliferation of bladder carcinoma, glioma, and hepatocellular carcinoma cells. Mechanistic analyses indicate GPC1 suppression drives ECM-mediated inhibition of TGF-β and p38 MAPK pathways, supporting GPCs as diagnostic and prognostic candidates.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages17

Reading Time43 min

AccessFree to download

Keywords

Glypicans and tumorigenic involvement

TCGA pan-cancer expression findings (GPC1–6)

Prognostic association of GPC1

Experimental attenuation of proliferation (CRISPR/siRNA/anti-GPC1)

Mechanistic pathway analysis (ECM, TGF-β, p38 MAPK)

[www.oncotarget.com](www.oncotarget.com) Oncotarget, 2023, Vol. 14, pp: 219-235 Research Paper Attenuation of cancer proliferation by suppression of glypican-1 and its pleiotropic effects in neoplastic behavior Fang Cheng1, Victor Chérouvrier Hansson1, Grigorios Georgolopoulos2 and Katrin Mani1 1 Department of Experimental Medical Science, Glycobiology Group, Lund University, Biomedical Center A13, Lund, Sweden 2Genevia Technologies Oy, Tampere 33100, Finland Correspondence to: Katrin Mani, email: [katrin.mani@med.lu.se](katrin.mani@med.lu.se) Keywords: Glypican-1; TCGA; bladder carcinoma; hepatocellular carcinoma; glioma Received: March 01, 2023 Accepted: March 08, 2023 Published: March 21, 2023 Copyright: © 2023 Cheng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Glypicans (GPC1-6) are associated with tumorigenic processes and their involvement in neoplastic behavior has been discussed in different cancer types. Here, a cancer-wide GPC expression study, using clinical cancer patient data in The Cancer Genome Atlas, reveals net upregulation of GPC1 and GPC2 in primary solid tumors, whereas GPC3, GPC5 and GPC6 display lowered expression pattern compared to normal tissues. Focusing on GPC1, survival analyses of the clinical cancer patient data reveal statistically significant correlation between high expression of GPC1 and poor prognosis in 10 particular cancer types i.e., bladder urothelial carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, colon adenocarcinoma, kidney renal clear cell carcinoma, lung adenocarcinoma, mesothelioma, ovarian serous cystadenocarcinoma, uterine corpus endometrial carcinoma and uveal melanoma. In vitro studies targeting GPC1 expression by CRISPR/Cas9 or siRNA or treatment with an anti-GPC1 antibody resulted in attenuation of proliferation of cancer cells from bladder carcinoma, glioma and hepatocellular carcinoma patients (T24, U87 and HepG2 cells) . Further, overexpression of GPC1 exhibited a significant and negative correlation between GPC1 expression and proliferation of T24 cells. Attempt to reveal the mechanism through which downregulation of GPC1 leads to attenuation of tumor growth using systematic Ingenuity Pathway Analysis indicate that suppression of GPC1 results in ECM-mediated inhibition of specific pro-cancer signaling pathways involving TGF-β and p38 MAPK. Identified differential expression and pleiotropic effects of GPCs in specific cancer types emphasize their potential of as novel diagnostic tools and prognostic factors and open doors for future GPC targeted therapy. INTRODUCTION The environment surrounding a tumor contains various components that influence growth and spread of cancer. These components include: proliferating cancer cells, inflammatory cells that have infiltrated the area, structural support provided by the tumor stroma, blood vessels, and various signaling molecules and matrix components that are secreted by the tumor and its surrounding cells. Aberrant growth factor signaling, insensitivity to growth-inhibitory signals, persistent angiogenesis and capability to invade tissues are results of alterations in cell physiology that give rise to malignant behavior. Glypicans (GPCs) are GPI anchored proteins attached to the outer leaflet of the cell membrane and act as co-receptors for different signaling molecules known for regulation of cell growth, motility and differentiation [1] . Six glypican isoforms (GPC1-6) have been identified in human cells. Intense research on the role of individual GPC in specific cancers has revealed new insights in the mechanisms of action and roles in neoplastic behavior [1–3] . Recent data from retrospective and prospective clinical studies point out the therapeutic value of GPCs, as

FAQs

What does the study report about GPC1 and other glypican isoforms across cancers?

It finds net upregulation of GPC1 and GPC2 in primary solid tumors, while GPC3, GPC5, and GPC6 show lowered expression compared with normal tissues.

How is GPC1 associated with patient prognosis in specific cancers?

Survival analyses show statistically significant correlation between high GPC1 expression and poor prognosis in 10 listed cancer types, including bladder urothelial carcinoma and hepatocellular carcinoma.

What experimental approaches were used to test the effect of suppressing GPC1 on cancer cell proliferation?

The study suppresses GPC1 using CRISPR/Cas9, siRNA, or an anti-GPC1 antibody, resulting in attenuation of proliferation in cancer cell lines derived from bladder carcinoma, glioma, and hepatocellular carcinoma.

Sep 24, 2026

Uploaded by Himbo