The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells.

Biomolecules
Giovanna ButeraMassimo Donadelli

Abstract

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...Continue Reading

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Citations

Jul 2, 2020·Journal of Experimental & Clinical Cancer Research : CR·Alessia GarufiGabriella D'Orazi
Feb 7, 2021·Biomolecules·Gabriella D'Orazi
Oct 17, 2020·Journal of Hematology & Oncology·Julia López de AndrésJuan Antonio Marchal

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Methods Mentioned

BETA
Transfection
Assay
protein assay
biopsies

Software Mentioned

MSstats
SecretomeP
NIH Image J
DAVID
ClueGO app
Cytoscape
ClueGO
Umpire
DIA
Protein Pilot

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