The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells.
Giovanna ButeraJessica BrandiChiara CavalliniAldo ScarpaRita T LawlorMaria Teresa ScupoliEmílio MarengoDaniela CecconiMarcello ManfrediMassimo DonadelliPublished in: Biomolecules (2020)
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.
Keyphrases
- papillary thyroid
- epithelial mesenchymal transition
- cell cycle arrest
- squamous cell
- wild type
- induced apoptosis
- signaling pathway
- high resolution
- oxidative stress
- cell migration
- transcription factor
- poor prognosis
- lymph node metastasis
- gene expression
- coronary artery disease
- healthcare
- squamous cell carcinoma
- childhood cancer
- ms ms
- multiple sclerosis
- type diabetes
- risk factors
- social media
- high speed
- heat stress