---
title: "Pannexin 1 inhibition reduces glioblastoma tumorigenicity via HIPPO and Wnt pathways"
id: "biorxiv-12-pannexin-1-inhibition-reduces-tumorigenic-properties-of-patient-derived"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-12-pannexin-1-inhibition-reduces-tumorigenic-properties-of-patient-derived"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.03.749222v1?rss=1"
published_at: "2026-09-07T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Pannexin 1 inhibition reduces glioblastoma tumorigenicity via HIPPO and Wnt pathways
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-12-pannexin-1-inhibition-reduces-tumorigenic-properties-of-patient-derived
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.03.749222v1?rss=1)
- **Published At:** 2026-09-07T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- Glioblastoma (GBM) has poor prognosis with median survival of 12–18 months, motivating new targets. - The channel-forming glycoprotein **PANX1** is upregulated in GBM tissue and is broadly expressed across patient tumors. - Western blot of patient-derived GBM cell lines showed markedly higher **PANX1** levels compared with normal brain tissue and control glial cells. - CRISPR/Cas9 deletion produced PANX1 knockout (PANX1-KO) GBM cells for molecular and functional comparison with controls. - Bulk RNA-sequencing of PANX1-KO cells revealed altered expression of genes associated with cell surface and junction components and pathways, including the **HIPPO** pathway, and downregulation of **β-catenin** and elements of the **Wnt** pathway. - PANX1 loss disrupted **β-catenin** protein and caused pronounced reductions in cell migration and growth in vitro. - Pharmacological blockade with **Probenecid (PBN)** and **Spironolactone (SPIR)** decreased live GBM cell counts, reduced migration in scratch assays, and markedly reduced F-actin filament formation. - Treatment with PBN and SPIR altered cellular localization of **β-catenin**, making it more intracellular compared with controls. - In xenograft models, PBN treatment reduced tumor cell viability measured by bioluminescent imaging and decreased incidence of tumor hemorrhage. - Authors conclude that **PANX1** contributes to GBM tumorigenic properties via multiple signaling pathways and that PANX1 is a candidate therapeutic target warranting further study. - No competing interests were declared. Funding sources included the Canadian Institutes of Health Research and several cancer research foundations.
## Clinical Analysis & Structured Key Points
Pannexin 1 inhibition reduces tumorigenic properties of patient-derived glioblastoma cells through the HIPPO and Wnt signalling pathways | bioRxiv Skip to main content New Results Pannexin 1 inhibition reduces tumorigenic properties of patient-derived glioblastoma cells through the HIPPO and Wnt signalling pathways Danielle Johnston , Matthew Huver , Rehanna Kanji , Carlijn Van Kessel , John Kelly , View ORCID Profile Rafael E Sanchez Pupo , Brooke O'Donnell , Norah Defamie , Rebecca Lau , Carolina Herrera , Andrew Deweyert , Marc Mesnil , View ORCID Profile John Ronald , Matthew Hebb , View ORCID Profile Silvia Penuela doi: https://doi.org/10.64898/2026.09.03.749222 Danielle Johnston 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Matthew Huver 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rehanna Kanji 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Carlijn Van Kessel 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site John Kelly 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rafael E Sanchez Pupo 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Rafael E Sanchez Pupo Brooke O'Donnell 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Norah Defamie 2 University of Poitiers; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rebecca Lau 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Carolina Herrera 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Andrew Deweyert 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Marc Mesnil 2 University of Poitiers; Find this author on Google Scholar Find this author on PubMed Search for this author on this site John Ronald 3 The University of Western Ontario; Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for John Ronald Matthew Hebb 1 Western University; Find this author on Google Scholar Find this author on PubMed Search for this author on this site Silvia Penuela 4 University of Western Ontario Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Silvia Penuela For correspondence: spenuela{at}uwo.ca Abstract Info/History Metrics Supplementary material Preview PDF Abstract Glioblastoma (GBM) is the most common primary brain tumour, with a median survival of 12-18 months, highlighting a need for new treatment targets. We observed that pannexin 1 (PANX1), a channel-forming glycoprotein important in purinergic signalling, is upregulated in GBM compared to normal tissue and expressed throughout patient tumours. Western blot analysis of patient-derived GBM cell lines revealed significantly increased PANX1 expression in these primary lines compared to brain tissue and control glial cells. Bulk RNA-sequencing compared the gene expression of GBM cells devoid of PANX1 via CRISPR/Cas9 deletion (PANX1-KO) compared to controls. Gene Ontology and KEGG gene set analyses revealed PANX1-KO in GBM cells affects cell surface and cell junction components, processes, and pathways, including the HIPPO pathway, in addition to critically downregulating β-catenin mRNA and other components of the Wnt pathway. The deletion of PANX1 resulted in a disruption of the β-catenin protein and a dramatic reduction in migration and cell growth. Pharmacological inhibition of PANX1 in GBM cells with Probenecid (PBN) and Spironolactone (SPIR) demonstrated a significant reduction in live cell numbers and migration via scratch assay. Both blockers dramatically decreased F-actin filament formation, and the cellular localization of beta-catenin became more intracellular compared to controls. Xenografted GBM tumours showed a reduction in tumour cell viability by bioluminescent imaging and reduced hemorrhaging incidence when treated with PBN. These new insights support further investigation of PANX1 as a potential GBM therapeutic target and its role in multiple cancer signaling pathways that regulate this devastating disease. Competing Interest Statement The authors have declared no competing interest. Funder Information Declared Canadian Institutes of Health Research, https://ror.org/01gavpb45 , PJT 185953 , Catalyst grant from London Cancer Research Program (LRCP) , Brain Tumour Foundation , Ligue contre le Cancer, Comité de la Vienne Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. Back to top Previous Posted September 07, 2026. Download PDF Supplementary Material Email Thank you for your interest in spreading the word about bioRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. Your Email * Your Name * Send To * Enter multiple addresses on separate lines or separate them with commas. 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