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08 04, 2021;16 (1): 11.

NUAK2 and RCan2 participate in the p53 mutant pro-tumorigenic network.

Eleonora Mammarella, Carlotta Zampieri, Emanuele Panatta, Gerry Melino, Ivano Amelio
Author Information
  1. Eleonora Mammarella: Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy.
  2. Carlotta Zampieri: Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. ORCID
  3. Emanuele Panatta: Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. ORCID
  4. Gerry Melino: Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. ORCID
  5. Ivano Amelio: Department of Experimental Medicine, TOR, University of Rome Tor Vergata, 00133, Rome, Italy. ivano.amelio@uniroma2.it. ORCID
PMID: 34348766 DOI: 10.1186/s13062-021-00296-5

Abstract

Most inactivating mutations in TP53 gene generates neomorphic forms of p53 proteins that experimental evidence and clinical observations suggest to exert gain-of-function effects. While massive effort has been deployed in the dissection of wild type p53 transcriptional programme, p53 mutant pro-tumorigenic gene network is still largely elusive. To help dissecting the molecular basis of p53 mutant GOF, we performed an analysis of a fully annotated genomic and transcriptomic human pancreatic adenocarcinoma to select candidate players of p53 mutant network on the basis their differential expression between p53 mutant and p53 wild-type cohorts and their prognostic value. We identified NUAK2 and RCan2 whose p53 mutant GOF-dependent regulation was further validated in pancreatic cancer cellular model. Our data demonstrated that p53 can physically bind RCan2 gene locus in regulatory regions corresponding to the chromatin permissive areas where known binding partners of p53 mutant, such as p63 and Srebp, bind. Overall, starting from clinically relevant data and progressing into experimental validation, our work suggests NUAK2 and RCan2 as novel candidate players of the p53 mutant pro-tumorigenic network whose prognostic and therapeutic interest might attract future studies.

Keywords

Cancer prognosis Metastasis Tumour progression Tumour suppression

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MeSH Term

Animals
Carcinogenesis
Cell Line, Tumor
Gene Regulatory Networks
Genes, p53
Humans
Mice
Muscle Proteins
Pancreatic Neoplasms
Protein Serine-Threonine Kinases
Tumor Suppressor Protein p53
Pancreatic Neoplasms

Chemicals

Muscle Proteins
RCAN2 protein, human
TP53 protein, human
Tumor Suppressor Protein p53
NUAK2 protein, human
Protein Serine-Threonine Kinases
Journal Article Research Support, Non-U.S. Gov't
Article has an altmetric score of 2

Word Cloud

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