Pannexin 1 binds β-catenin to modulate melanoma cell growth and metabolism
| Autor: | Kenneth Huang, Lina Dagnino, Danielle Johnston, Alexandra M. Kozlov, David B. Sacks, Dean H. Betts, Zhigang Li, Christopher Zhang, Samar Sayedyahossein, Silvia Penuela, Daniel Nouri-Nejad |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
LEF1 lymphoid enhancer-binding factor 1 DMEM Dulbecco's modified Eagle medium Cell Biochemistry Pediatrics Connexins Cell Movement PANX1 Melanoma Wnt Signaling Pathway beta Catenin Chemistry Cell Cycle Wnt signaling pathway Pannexin Microphthalmia-associated transcription factor ATCC American-type culture collection 3. Good health Cell biology mitochondria medicine.anatomical_structure Research Article MBP maltose-binding protein malignant melanoma PANX1 pannexin 1 PBS phosphate-buffered saline MITF microphthalmia-associated transcription factor Nerve Tissue Proteins 03 medical and health sciences Wnt Cell Line Tumor medicine Animals Humans Molecular Biology Transcription factor Cell Proliferation KO knockout 030102 biochemistry & molecular biology EDTA ethylenediaminetetraacetic acid Cell growth Cell Biology β-catenin medicine.disease BCA bicinchoninic acid 030104 developmental biology Catenin pannexin TCGA The Cancer Genome Atlas Transcription Factors |
| Zdroj: | Paediatrics Publications The Journal of Biological Chemistry |
| Popis: | Melanoma is the most aggressive skin malignancy with increasing incidence worldwide. Pannexin1 (PANX1), a member of the pannexin family of channel-forming glycoproteins, regulates cellular processes in melanoma cells including proliferation, migration, and invasion/metastasis. However, the mechanisms responsible for coordinating and regulating PANX1 function remain unclear. Here, we demonstrated a direct interaction between the C-terminal region of PANX1 and the N-terminal portion of β-catenin, a key transcription factor in the Wnt pathway. At the protein level, β-catenin was significantly decreased when PANX1 was either knocked down or inhibited by two PANX1 blockers, Probenecid and Spironolactone. Immunofluorescence imaging showed a disrupted pattern of β-catenin localization at the cell membrane in PANX1-deficient cells, and transcription of several Wnt target genes, including MITF, was suppressed. In addition, a mitochondrial stress test revealed that the metabolism of PANX1-deficient cells was impaired, indicating a role for PANX1 in the regulation of the melanoma cell metabolic profile. Taken together, our data show that PANX1 directly interacts with β-catenin to modulate growth and metabolism in melanoma cells. These findings provide mechanistic insight into PANX1-mediated melanoma progression and may be applicable to other contexts where PANX1 and β-catenin interact as a potential new component of the Wnt signaling pathway. |
| Databáze: | OpenAIRE |
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