Tumor Suppressor Role of Wild-Type P53-Dependent Secretome and Its Proteomic Identification in PDAC

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2022-02, Vol.12 (2), p.305
• Main Authors: Butera, Giovanna, Manfredi, Marcello, Fiore, Alessandra, Brandi, Jessica, Pacchiana, Raffaella, De Giorgis, Veronica, Barberis, Elettra, Vanella, Virginia, Galasso, Marilisa, Scupoli, Maria Teresa, Marengo, Emilio, Cecconi, Daniela, Donadelli, Massimo
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Apoptosis; Biomarkers; Biotechnology; Cancer; Carcinoma, Pancreatic Ductal - metabolism; Cell adhesion & migration; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation; Humans; Invasiveness; Microenvironments; Mutation; onco-suppressor gene; p53 Protein; Pancreatic cancer; pancreatic ductal adenocarcinoma; Pancreatic Neoplasms; Pancreatic Neoplasms - metabolism; Proteins; Proteomics; Roles; Secretome; Tumor Microenvironment; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Tumorigenesis; wild-type p53
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom12020305

The study of the cancer secretome is gaining even more importance in cancers such as pancreatic ductal adenocarcinoma (PDAC), whose lack of recognizable symptoms and early detection assays make this type of cancer highly lethal. The wild-type p53 protein, frequently mutated in PDAC, prevents tumorigenesis by regulating a plethora of signaling pathways. The importance of the p53 tumor suppressive activity is not only primarily involved within cells to limit tumor cell proliferation but also in the extracellular space. Thus, loss of p53 has a profound impact on the secretome composition of cancer cells and marks the transition to invasiveness. Here, we demonstrate the tumor suppressive role of wild-type p53 on cancer cell secretome, showing the anti-proliferative, apoptotic and chemosensitivity effects of wild-type p53 driven conditioned medium. By using high-resolution SWATH-MS technology, we characterized the secretomes of p53-deficient and p53-expressing PDAC cells. We found a great number of secreted proteins that have known roles in cancer-related processes, 30 of which showed enhanced and 17 reduced secretion in response to p53 silencing. These results are important to advance our understanding on the link between wt-p53 and cancer microenvironment. In conclusion, this approach may detect a secreted signature specifically driven by wild-type p53 in PDAC.