Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells
Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of...
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MDPI AG
2019-01-01
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| Series: | Cancers |
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| Online Access: | http://www.mdpi.com/2072-6694/11/1/102 |
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doaj-e3546e7986d94de9a73bf6a817e968ac2020-11-25T01:38:53ZengMDPI AGCancers2072-66942019-01-0111110210.3390/cancers11010102cancers11010102Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma CellsTaylor J. Freeman0Samar Sayedyahossein1Danielle Johnston2Rafael E. Sanchez-Pupo3Brooke O’Donnell4Kenneth Huang5Zameena Lakhani6Daniel Nouri-Nejad7Kevin J. Barr8Luke Harland9Steven Latosinsky10Aaron Grant11Lina Dagnino12Silvia Penuela13Department of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaSurgery, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaSurgery, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaPhysiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaDepartment of Anatomy and Cell Biology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, ON N6A5C1, CanadaPannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment of A375-MA2 tumors in chicken embryo xenografts with CBX or PBN significantly reduced melanoma tumor weight and invasiveness. Blocking PANX1 channels with PBN reduced ATP release in A375-P cells, suggesting a potential role for PANX1 in purinergic signaling of melanoma cells. In addition, cell-surface biotinylation assays indicate that there is an intracellular pool of PANX1 in melanoma cells. PANX1 likely modulates signaling through the Wnt/β-catenin pathway, because β-catenin levels were significantly decreased upon PANX1 silencing. Collectively, our findings identify a role for PANX1 in controlling growth and tumorigenic properties of melanoma cells contributing to signaling pathways that modulate melanoma progression.http://www.mdpi.com/2072-6694/11/1/102pannexinPANX1melanomacarbenoxoloneprobenecidtumor growthpatient-derived cellsChick-CAMxenograftsATPWntβ-catenin |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Taylor J. Freeman Samar Sayedyahossein Danielle Johnston Rafael E. Sanchez-Pupo Brooke O’Donnell Kenneth Huang Zameena Lakhani Daniel Nouri-Nejad Kevin J. Barr Luke Harland Steven Latosinsky Aaron Grant Lina Dagnino Silvia Penuela |
| spellingShingle |
Taylor J. Freeman Samar Sayedyahossein Danielle Johnston Rafael E. Sanchez-Pupo Brooke O’Donnell Kenneth Huang Zameena Lakhani Daniel Nouri-Nejad Kevin J. Barr Luke Harland Steven Latosinsky Aaron Grant Lina Dagnino Silvia Penuela Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells Cancers pannexin PANX1 melanoma carbenoxolone probenecid tumor growth patient-derived cells Chick-CAM xenografts ATP Wnt β-catenin |
| author_facet |
Taylor J. Freeman Samar Sayedyahossein Danielle Johnston Rafael E. Sanchez-Pupo Brooke O’Donnell Kenneth Huang Zameena Lakhani Daniel Nouri-Nejad Kevin J. Barr Luke Harland Steven Latosinsky Aaron Grant Lina Dagnino Silvia Penuela |
| author_sort |
Taylor J. Freeman |
| title |
Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells |
| title_short |
Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells |
| title_full |
Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells |
| title_fullStr |
Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells |
| title_full_unstemmed |
Inhibition of Pannexin 1 Reduces the Tumorigenic Properties of Human Melanoma Cells |
| title_sort |
inhibition of pannexin 1 reduces the tumorigenic properties of human melanoma cells |
| publisher |
MDPI AG |
| series |
Cancers |
| issn |
2072-6694 |
| publishDate |
2019-01-01 |
| description |
Pannexin 1 (PANX1) is a channel-forming glycoprotein expressed in many tissues including the skin. PANX1 channels allow the passage of ions and molecules up to 1 kDa, including ATP and other metabolites. In this study, we show that PANX1 is highly expressed in human melanoma tumors at all stages of disease progression, as well as in patient-derived cells and established melanoma cell lines. Reducing PANX1 protein levels using shRNA or inhibiting channel function with the channel blockers, carbenoxolone (CBX) and probenecid (PBN), significantly decreased cell growth and migration, and increased melanin production in A375-P and A375-MA2 cell lines. Further, treatment of A375-MA2 tumors in chicken embryo xenografts with CBX or PBN significantly reduced melanoma tumor weight and invasiveness. Blocking PANX1 channels with PBN reduced ATP release in A375-P cells, suggesting a potential role for PANX1 in purinergic signaling of melanoma cells. In addition, cell-surface biotinylation assays indicate that there is an intracellular pool of PANX1 in melanoma cells. PANX1 likely modulates signaling through the Wnt/β-catenin pathway, because β-catenin levels were significantly decreased upon PANX1 silencing. Collectively, our findings identify a role for PANX1 in controlling growth and tumorigenic properties of melanoma cells contributing to signaling pathways that modulate melanoma progression. |
| topic |
pannexin PANX1 melanoma carbenoxolone probenecid tumor growth patient-derived cells Chick-CAM xenografts ATP Wnt β-catenin |
| url |
http://www.mdpi.com/2072-6694/11/1/102 |
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