The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells
The cancer secretome is a rich repository of useful information for both cancer biology and clinical oncology. A better understanding of cancer secretome is particularly relevant for pancreatic ductal adenocarcinoma (PDAC), whose extremely high mortality rate is mainly due to early metastasis, resis...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/6/884 |
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| author | Giovanna Butera Jessica Brandi Chiara Cavallini Aldo Scarpa Rita T. Lawlor Maria Teresa Scupoli Emílio Marengo Daniela Cecconi Marcello Manfredi Massimo Donadelli |
| author_facet | Giovanna Butera Jessica Brandi Chiara Cavallini Aldo Scarpa Rita T. Lawlor Maria Teresa Scupoli Emílio Marengo Daniela Cecconi Marcello Manfredi Massimo Donadelli |
| author_sort | Giovanna Butera |
| collection | DOAJ |
| description | The cancer secretome is a rich repository of useful information for both cancer biology and clinical oncology. A better understanding of cancer secretome is particularly relevant for pancreatic ductal adenocarcinoma (PDAC), whose extremely high mortality rate is mainly due to early metastasis, resistance to conventional treatments, lack of recognizable symptoms, and assays for early detection. TP53 gene is a master transcriptional regulator controlling several key cellular pathways and it is mutated in ~75% of PDACs. We report the functional effect of the hot-spot p53 mutant isoforms R175H and R273H on cancer cell secretome, showing their influence on proliferation, chemoresistance, apoptosis, and autophagy, as well as cell migration and epithelial-mesenchymal transition. We compared the secretome of p53-null AsPC-1 PDAC cells after ectopic over-expression of R175H-mutp53 or R273H-mutp53 to identify the differentially secreted proteins by mutant p53. By using high-resolution SWATH-MS technology, we found a great number of differentially secreted proteins by the two p53 mutants, 15 of which are common to both mutants. Most of these secreted proteins are reported to promote cancer progression and epithelial-mesenchymal transition and might constitute a biomarker secreted signature that is driven by the hot-spot p53 mutants in PDAC. |
| first_indexed | 2024-03-10T19:18:28Z |
| format | Article |
| id | doaj.art-f0a32508d8924c51bad19315609e0b28 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T19:18:28Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-f0a32508d8924c51bad19315609e0b282023-11-20T03:15:46ZengMDPI AGBiomolecules2218-273X2020-06-0110688410.3390/biom10060884The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma CellsGiovanna Butera0Jessica Brandi1Chiara Cavallini2Aldo Scarpa3Rita T. Lawlor4Maria Teresa Scupoli5Emílio Marengo6Daniela Cecconi7Marcello Manfredi8Massimo Donadelli9Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, ItalyDepartment of Biotechnology, University of Verona, 37134 Verona, ItalyResearch Center LURM (Interdepartmental Laboratory of Medical Research), University of Verona, 37134 Verona, ItalyDepartment of Diagnostics and Public health, Section of Pathology, University of Verona, 37134 Verona, ItalyARC-Net Centre for Applied Research on Cancer, University and Hospital Trust of Verona, 37134 Verona, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, ItalyDepartment of Sciences and Technological Innovation, University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Biotechnology, University of Verona, 37134 Verona, ItalyCenter for Translational Research on Autoimmune and Allergic Diseases, University of Piemonte Orientale, Italy, ISALIT, Spin-off at the University of Piemonte Orientale, 28100 Novara, ItalyDepartment of Neurosciences, Biomedicine and Movement Sciences, Section of Biochemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, ItalyThe cancer secretome is a rich repository of useful information for both cancer biology and clinical oncology. A better understanding of cancer secretome is particularly relevant for pancreatic ductal adenocarcinoma (PDAC), whose extremely high mortality rate is mainly due to early metastasis, resistance to conventional treatments, lack of recognizable symptoms, and assays for early detection. TP53 gene is a master transcriptional regulator controlling several key cellular pathways and it is mutated in ~75% of PDACs. We report the functional effect of the hot-spot p53 mutant isoforms R175H and R273H on cancer cell secretome, showing their influence on proliferation, chemoresistance, apoptosis, and autophagy, as well as cell migration and epithelial-mesenchymal transition. We compared the secretome of p53-null AsPC-1 PDAC cells after ectopic over-expression of R175H-mutp53 or R273H-mutp53 to identify the differentially secreted proteins by mutant p53. By using high-resolution SWATH-MS technology, we found a great number of differentially secreted proteins by the two p53 mutants, 15 of which are common to both mutants. Most of these secreted proteins are reported to promote cancer progression and epithelial-mesenchymal transition and might constitute a biomarker secreted signature that is driven by the hot-spot p53 mutants in PDAC.https://www.mdpi.com/2218-273X/10/6/884mutant p53pancreatic adenocarcinomasecretomeproteomicsoncogenesgain-of-function |
| spellingShingle | Giovanna Butera Jessica Brandi Chiara Cavallini Aldo Scarpa Rita T. Lawlor Maria Teresa Scupoli Emílio Marengo Daniela Cecconi Marcello Manfredi Massimo Donadelli The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells Biomolecules mutant p53 pancreatic adenocarcinoma secretome proteomics oncogenes gain-of-function |
| title | The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells |
| title_full | The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells |
| title_fullStr | The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells |
| title_full_unstemmed | The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells |
| title_short | The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells |
| title_sort | mutant p53 driven secretome has oncogenic functions in pancreatic ductal adenocarcinoma cells |
| topic | mutant p53 pancreatic adenocarcinoma secretome proteomics oncogenes gain-of-function |
| url | https://www.mdpi.com/2218-273X/10/6/884 |
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