A piece of the p53 puzzle

Bieging, Kathryn T.; Attardi, Laura D.

doi:10.1038/nature14374

Cited by 14 publications

(15 citation statements)

References 11 publications

(9 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Besides, the major tumor suppressor protein p53 is one of the most frequently mutated tumor suppressors identified so far in human cancers, and stable expression of p53 is crucial for its tumor suppressor function [28,29]. Our results showed that compound 1 could obviously up-regulate the expression level of p53 ( Figure 5C), which further supported compound 1 to be a candidate for cancer treatment.…”

Section: Pro-apoptotic and P53 Suppressing Activities Of Compoundsupporting

confidence: 62%

Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells

et al. 2016

View full text Add to dashboard Cite

Abstract:The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R-T (1-3) and caesalsappanins M and N (4 and 5), together with seven known compounds 6-12. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute configurations of compounds 1 and 4 were determined by the corresponding CD spectra. All the isolated compounds were tested for their cytotoxicity against ovarian cancer A2780 and HEY, gastric cancer AGS, and non-small cell lung cancer A549 cells. Compound 1 displayed significant toxicity against the four cell lines with the IC 50 values of 9.9˘1.6 µM, 12.2˘6.5 µM, 5.3˘1.9 µM, and 12.3˘3.1 µM, respectively. Compound 1 induced G1 phase cell cycle arrest in A2780 cells. Furthermore, compound 1 dose-dependently induced A2780 cells apoptosis as evidenced by Hoechst 33342 staining, Annexin V positive cells, the up-regulated cleaved-PARP and the enhanced Bax/Bcl-2 ratio. What's more, compound 1 also promoted the expression of the tumor suppressor p53 protein. These findings indicate that cassane diterpenoids might have potential as anti-cancer agents, and further in vivo animal studies and structural modification investigation are needed.

show abstract

Section: Pro-apoptotic and P53 Suppressing Activities Of Compoundsupporting

confidence: 62%

Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells

et al. 2016

View full text Add to dashboard Cite

show abstract

“…A discussion of all aspects of the various signaling pathways regulated by TP53 is beyond the scope of this article and recent reviews on this subject are available (12,20,21).…”

Section: The Tp53 Networkmentioning

confidence: 99%

Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice

et al. 2017

View full text Add to dashboard Cite

Accurate assessment of TP53 gene status in sporadic tumors and in the germline of individuals at high risk of cancer due to Li-Fraumeni Syndrome (LFS) has important clinical implications for diagnosis, surveillance, and therapy. Genomic data from more than 20,000 cancer genomes provide a wealth of information on cancer gene alterations and have confirmed TP53 as the most commonly mutated gene in human cancer. Analysis of a database of 70,000 TP53 variants reveals that the two newly discovered exons of the gene, exons 9b and 9g, generated by alternative splicing, are the targets of inactivating mutation events in breast, liver, and head and neck tumors. Furthermore, germline rearrangements in intron 1 of TP53 are associated with LFS and are frequently observed in sporadic osteosarcoma. In this context of constantly growing genomic data, we discuss how screening strategies must be improved when assessing TP53 status in clinical samples. Finally, we discuss how TP53 alterations should be described by using accurate nomenclature to avoid confusion in scientific and clinical reports.

show abstract

“…The gain-of-function (GOF) properties of mutant p53 have partially been explained by its ability to physically interact with other transcriptional factors and deregulate their transcriptional abilities ( 6 – 9 ). Indeed, although canonical p53-mediated tumor suppression is strictly related to cell cycle arrest/apoptosis, accumulating evidence highlights the involvement of mutant forms of p53 in processes such as cancer metabolism, invasion/metastasis, and tumor microenvironment interactions ( 10 , 11 ). However, understanding of the impact of p53 mutants in different cellular, mutational, and microenvironmental backgrounds is limited; despite this, it would be critical to dissect the basis of the oncogenic phenotype associated with mutant p53 and consequentially accelerate improvement of the management of oncological patients.…”

mentioning

confidence: 99%

p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression

Amelio

Mancini

Petrova

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

102

View full text Add to dashboard Cite

SignificanceExpression in cancer cells of novel proteins generated by mutations in the TP53 gene is an important prognostic factor; however, how p53 mutants promote cancer progression is largely unknown. Here, we describe a molecular mechanism of gain-of-function by mutant p53 in hypoxic non-small cell lung cancer (NSCLC) cells. We identified the existence of a hypoxia-inducible factor-1 (HIF-1)/mutant p53 complex, exerting transcriptional control of a specific subset of protumorigenic genes, codifying for extracellular matrix (ECM) components. Employing in vivo cancer models and analyzing clinical material, we demonstrate that these ECM components substantially contribute to the synergistic protumorigenic activity of p53 mutants and HIF-1. Our data indicate that HIF-1/mutant p53 cross-talk is an innovative potential therapeutic target to treat advanced NSCLC.

show abstract

A piece of the p53 puzzle

Cited by 14 publications

References 11 publications

Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells

Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells

Recommended Guidelines for Validation, Quality Control, and Reporting of TP53 Variants in Clinical Practice

p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression

Contact Info

Product

Resources

About