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Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition
Abstract
Mutations in TP53 gene play a pivotal role in tumorigenesis and cancer development. Here, we report that gain‐of‐function mutant p53 proteins inhibit the autophagic pathway favoring antiapoptotic effects as well as proliferation of pancreas and breast cancer cells. We found that mutant p53 significantly counteracts the formation of autophagic vesicles and their fusion with lysosomes throughout the repression of some key autophagy‐related proteins and enzymes as BECN1 (and P‐BECN1), DRAM1, ATG12, SESN1/2 and P‐AMPK with the concomitant stimulation of mTOR signaling. As a paradigm of this mechanism, we show that atg12 gene repression was mediated by the recruitment of the p50 NF‐κB/mutant p53 protein complex onto the atg12 promoter. Either mutant p53 or p50 NF‐κB depletion downregulates atg12 gene expression. We further correlated the low expression levels of autophagic genes (atg12, becn1, sesn1, and dram1) with a reduced relapse free survival (RFS) and distant metastasis free survival (DMFS) of breast cancer patients carrying TP53 gene mutations conferring a prognostic value to this mutant p53‐and autophagy‐related signature. Interestingly, the mutant p53‐driven mTOR stimulation sensitized cancer cells to the treatment with the mTOR inhibitor everolimus. All these results reveal a novel mechanism through which mutant p53 proteins promote cancer cell proliferation with the concomitant inhibition of autophagy.
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“In regulatory regions of the Atg12 promoter, mutant p53 can recruit the nuclear factor-kappa B (NF-κB) p50‒p50 homodimer to form a mutant p53‒p50 complex that inhibits Atg12 and blocks the autophagic process.165”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [165]
In the citing paper
“Mutant p53 inhibits autophagy by decreasing the mRNA or protein levels of Sestrins, preventing the activation of the AMPK signaling pathway and the formation of autophagic vesicles.165”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [165]
In the citing paper
“Mutant p53 affects the mTOR signaling pathway by reducing the level of Beclin-1 phosphorylation to suppress autophagy.165”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [165]
In the citing paper
“Mutant p53 has been proven to inhibit autophagy via different mechanisms.163–166”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [165]
In the citing paper
“Mutant p53 also inhibits autophagy by stimulating mTOR signaling.114,165”
From p53: from understanding its structure to advances in therapeutic targeting (2026) · cites this paper as [165]
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Cites
Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).
Klionsky, D. J., Abdelmohsen, K., Abe, A., Abedin, M. J., Abeliovich, H., Acevedo Arozena, A., Adachi, H., Adams, C. M., Adams, P. D., Adeli, K., et al. (2016) · Autophagy · doi:10.1080/15548627.2015.1100356 · Cited by 5,894
Self-citationGyörffy, B., Lanczky, A., Eklund, A. C., Denkert, C., Budczies, J., Li, Q., & Szallasi, Z. (2010) · Breast Cancer Research and Treatment · doi:10.1007/s10549-009-0674-9 · Cited by 4,169
Whole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · cited 1×
“Introduction In the presentwork, we ascertain that GOFmutant p53 pro- Mutations in the TP53 gene occur in over 50% of human cancers, where most of them are missense mutations resulting in the expression of mutant forms of p53 (Vousden and Lu, 2002; Waddell et al., 2015).”
BackgroundGalluzzi, L., Vitale, I., Abrams, J. M., Alnemri, E. S., Baehrecke, E. H., Blagosklonny, M. V., Dawson, T. M., Dawson, V. L., El-Deiry, W. S., Fulda, S., et al. (2012) · Cell Death & Differentiation · doi:10.1038/cdd.2011.96 · Cited by 2,421
p53 Target Genes Sestrin1 and Sestrin2 Connect Genotoxic Stress and mTOR Signaling
Budanov, A. V., & Karin, M. (2008) · Cell · doi:10.1016/j.cell.2008.06.028 · Cited by 1,326 · cited 2×
“We further documented that mutant p53 suppressed the expression of Sestrins which have been described to act as AMPK activators through the direct interaction with AMPK complex favoring its phosphorylation by upstream kinases (Budanov and Karin, 2008; Morrison et al., 2015; Sanli et al., 2012).”
BackgroundDi Agostino, S., Strano, S., Emiliozzi, V., Zerbini, V., Mottolese, M., Sacchi, A., Blandino, G., & Piaggio, G. (2006) · Cancer Cell · doi:10.1016/j.ccr.2006.08.013 · Cited by 418
Self-citationModulation of the Vitamin D3 Response by Cancer-Associated Mutant p53
Stambolsky, P., Tabach, Y., Fontemaggi, G., Weisz, L., Maor-Aloni, R., Sigfried, Z., Shiff, I., Kogan, I., Shay, M., Kalo, E., et al. (2010) · Cancer Cell · doi:10.1016/j.ccr.2009.11.025 · Cited by 245
Self-citationElsharkawy, A. M., Oakley, F., Lin, F., Packham, G., Mann, D. A., & Mann, J. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.03.025 · Cited by 160 · cited 1×
“As NF-kB p50 usually acts as a transcriptional repressor (Elsharkawy et al., 2010; Tong et al., 2004), we studied its recruitment onto the atg12 promoter.”
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Research works printed but not linked: 54
- 10.1016/j.cell.2009.01.039 · DOI · Paper page
- 10.1016/j.breast.2013.07.005 · DOI · Paper page
- 10.1002/emmm.201201483 · DOI
- 10.1126/science.1068999 · DOI · Paper page
- 10.1016/S0378-1119(01)00696-5 · DOI · Paper page
- 10.4161/cc.24128 · DOI · Paper page
- 10.1016/j.febslet.2014.04.015 · DOI
- 10.4161/auto.3438 · DOI · Paper page
- 10.1016/j.cell.2012.02.032 · DOI · Paper page
- Di Agostino S., 2015, YAP enhances the pro-proliferative transcriptional activity of mutant p53 proteins, EMBO Rep
- 10.1016/j.freeradbiomed.2013.05.014 · DOI · Paper page
- 10.1101/gr.216102 · DOI · Paper page
- 10.1038/leu.2008.348 · DOI
- 10.1016/j.bbamcr.2014.12.016 · DOI
- 10.1016/j.bbamcr.2014.10.003 · DOI
- 10.1007/s10495-012-0790-6 · DOI
- 10.1016/j.cell.2011.12.017 · DOI · Paper page
- 10.1101/gad.190678.112 · DOI · Paper page
- 10.1038/onc.2014.458 · DOI · Paper page
- 10.15252/embj.201490784 · DOI · Paper page
- 10.1093/annonc/mdt380 · DOI
- 10.1016/j.ccr.2011.06.004 · DOI · Paper page
- 10.1007/s10549-011-1412-7 · DOI · Paper page
- 10.1038/onc.2014.461 · DOI
- 10.1002/mc.22278 · DOI
- 10.1074/jbc.M412180200 · DOI
- 10.1111/febs.13540 · DOI · Paper page
- 10.4049/jimmunol.171.4.1750 · DOI
- 10.1016/S0092-8674(00)81871-1 · DOI · Paper page
- 10.1016/j.ejca.2012.03.001 · DOI
- 10.1016/j.semcancer.2013.06.007 · DOI · Paper page
- 10.1038/ncomms3130 · DOI · Paper page
- 10.1101/gad.1545107 · DOI · Paper page
- 10.1080/15548627.2015.1055439 · DOI
- 10.1038/26506 · DOI · Paper page
- 10.1096/fj.14-258814 · DOI · Paper page
- 10.4161/cc.7.19.6751 · DOI · Paper page
- 10.1038/ncb2641 · DOI · Paper page
- 10.1038/nrm2858 · DOI · Paper page
- 10.1016/S1476-5586(04)80047-2 · DOI · Paper page
- 10.1038/ncb2757 · DOI · Paper page
- 10.1371/journal.pone.0032035 · DOI
- 10.1007/978-94-017-9211-0_5 · DOI
- 10.1016/j.canlet.2008.07.005 · DOI
- 10.1016/j.ccr.2007.10.001 · DOI · Paper page
- 10.1038/sj.onc.1210296 · DOI · Paper page
- 10.1023/B:MCBI.0000044394.66951.4d · DOI
- 10.4161/cc.10.24.18682 · DOI
- 10.18632/oncotarget.2587 · DOI
- 10.1016/j.bcp.2014.07.006 · DOI
- Vousden K.H., 2002, Live or let die: the cell's response to p53. Nature reviews, Cancer, 2, 594
- 10.1093/carcin/bgs232 · DOI · Paper page
- 10.1158/0008-5472.CAN-06-2425 · DOI · Paper page
- 10.1016/j.molcel.2014.04.024 · DOI · Paper page
Cited by
Gain-of-function mutant p53 in cancer progression and therapy
Zhang, C., Liu, J., Xu, D., Zhang, T., Hu, W., & Feng, Z. (2020) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjaa040 · Cited by 334
p53: from understanding its structure to advances in therapeutic targeting
Wang, W., Liu, X., Liu, H., Abolhassani, H., Yan, H., Zhang, H., & Wang, X. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02549-5 · Cited by 30
Metadata
- Authors
- Cordani, M., Oppici, E., Dando, I., Butturini, E., Dalla Pozza, E., Nadal-Serrano, M., Oliver, J., Roca, P., Mariotto, S., Cellini, B., Blandino, G., Palmieri, M., Di Agostino, S., & Donadelli, M.
- Venue
- Molecular Oncology
- Publisher
- Wiley
- Published
- 2016-04-12
- Volume
- 10
- Issue
- 7
- Pages
- 1008-1029
- ISSN
- 1574-7891
- 1878-0261
- Cited by
- 141
- References
- 8
- Language
- en
- Update notices
- correction (2025-03-10)
- Funders
- Italian Association for Cancer Research (AIRC)-Fondazione CariPaRo (C98C13000210007)
- University of Verona (B12I15002320003)
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- Cordani, M., Oppici, E., Dando, I., Butturini, E., Dalla Pozza, E., Nadal-Serrano, M., Oliver, J., Roca, P., Mariotto, S., Cellini, B., Blandino, G., Palmieri, M., Di Agostino, S., & Donadelli, M. (2016). Mutant p53 proteins counteract autophagic mechanism sensitizing cancer cells to mTOR inhibition. Molecular Oncology. https://doi.org/10.1016/j.molonc.2016.04.001
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