Aberrant environment and PS-binding to calnuc C-terminal tail drives exosomal packaging and its metastatic ability
| العنوان: | Aberrant environment and PS-binding to calnuc C-terminal tail drives exosomal packaging and its metastatic ability |
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| المؤلفون: | Ganesh Venkatraman, Anita Sjölander, Ravichandran Vignesh, Gopala Krishna Aradhyam, Suresh K. Rayala |
| المصدر: | Biochemical Journal. 478:2265-2283 |
| بيانات النشر: | Portland Press Ltd., 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Epithelial-Mesenchymal Transition, Intracellular pH, Phosphatidylserines, Exosomes, medicine.disease_cause, Biochemistry, Mice, chemistry.chemical_compound, Cell Movement, Tumor Cells, Cultured, Tumor Microenvironment, medicine, Animals, Humans, Nucleobindins, Secretion, Molecular Biology, Cell Proliferation, Chemistry, Cell migration, Cell Biology, Phosphatidylserine, Molten globule, Microvesicles, Cell biology, Mice, Inbred C57BL, Pancreatic Neoplasms, Cancer cell, Carcinoma, Squamous Cell, Female, Mouth Neoplasms, Carcinogenesis |
| الوصف: | The characteristic features of cancer cells are aberrant (acidic) intracellular pH and elevated levels of phosphatidylserine. The primary focus of cancer research is concentrated on the discovery of biomarkers directed towards early diagnosis and therapy. It has been observed that azoxymethane-treated mice demonstrate an increased expression of calnuc (a multi-domain, Ca2+- and DNA-binding protein) in their colon, suggesting it to be a good biomarker of carcinogenesis. We show that culture supernatants from tumor cells have significantly higher amounts of secreted calnuc compared to non-tumor cells, selectively packaged into exosomes. Exosomal calnuc is causal for epithelial–mesenchymal transition and atypical migration in non-tumor cells, which are key events in tumorigenesis and metastasis. In vitro studies reveal a significant affinity for calnuc towards phosphatidylserine, specifically to its C-terminal region, leading to the formation of ‘molten globule’ conformation. Similar structural changes are observed at acidic pH (pH 4), which demonstrates the role of the acidic microenvironment in causing the molten globule conformation and membrane interaction. On a precise note, we propose that the molten globule structure of calnuc caused by aberrant conditions in cancer cells to be the causative mechanism underlying its exosome-mediated secretion, thereby driving metastasis. |
| تدمد: | 1470-8728 0264-6021 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3a824cff5e931c92e9bbbe258c8433daTest https://doi.org/10.1042/bcj20210016Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3a824cff5e931c92e9bbbe258c8433da |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14708728 02646021 |
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