2. Academic Validation
  3. c-Myc Sustains Pancreatic Cancer Cell Survival and mutp53 Stability through the Mevalonate Pathway

c-Myc Sustains Pancreatic Cancer Cell Survival and mutp53 Stability through the Mevalonate Pathway

  • Biomedicines. 2022 Oct 5;10(10):2489. doi: 10.3390/biomedicines10102489.
Maria Anele Romeo 1,  Maria Saveria Gilardini Montani 1,  Andrea Arena 1,  Rossella Benedetti 1,  Gabriella D'Orazi 2 3,  Mara Cirone 1
Affiliations

Affiliations

  • 1 Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena 324, 00161 Rome, Italy.
  • 2 Department of Research, Advanced Diagnostics, and Technological Innovation, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00128 Rome, Italy.
  • 3 Department of Neurosciences, Imaging and Clinical Sciences, University G. D'Annunzio, Via dei Vestini 33, 66100 Chieti, Italy.
PMID: 36289751 DOI: 10.3390/biomedicines10102489
Abstract

It has been shown that wild-type (wt)p53 inhibits oncogene c-Myc while mutant (mut)p53 may transactivate it, with an opposite behavior that frequently occurs in the crosstalk of wt or mutp53 with molecules/pathways promoting carcinogenesis. Even if it has been reported that mutp53 sustains c-Myc, whether c-Myc could in turn influence mutp53 expression remains to be investigated. In this study, we found that pharmacological or genetic inhibition of c-Myc downregulated mutp53, impaired cell survival and increased DNA damage in pancreatic Cancer cells. At the molecular level, we observed that c-Myc inhibition reduced the expression of mevalonate kinase (MVK), a molecule belonging to the mevalonate pathway that-according to previous findings-can control mutp53 stability, and thus contributes to Cancer cell survival. In conclusion, this study unveils another criminal alliance between oncogenes, such as c-Myc and mutp53, that plays a key role in oncogenesis.

Keywords

DDR; c-Myc; mevalonate; mutp53; oxidative stress; pancreatic cancer.

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