The p53 family and the hypoxia-inducible factors (HIFs): determinants of cancer progression

Amelio, Ivano; Melino, Gerry

doi:10.1016/j.tibs.2015.04.007

Cited by 128 publications

(110 citation statements)

References 102 publications

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“…In addition to VEGF, PDGF, IL8, galectin 1, and FGF1 and FGF2 are potent angiogenic factors 392,433,434 , among many others. Not surprisingly, many pro-angiogenic genes are direct HIF-1 targets via HREs in their promoters 435–439 .…”

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

“…p53, which is a target for the HPV E6 oncoprotein, antagonizes the HIF-1 pathway (reviewed in 435 ). p53 is stabilized by hypoxia and metabolic stress 487–491 , although the mechanisms and consequences are controversial 488,490–497 .…”

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

“…p53 is stabilized by hypoxia and metabolic stress 487–491 , although the mechanisms and consequences are controversial 488,490–497 . p53 binds and destabilizes HIF- 1α 435,483,487–489,492,498–502 . p53 also represses HIF-1-dependent transcription at some genes, including VEGF and metabolic genes such as carbonic anhydrase IX 435,483,500,501,503–507 .…”

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

“…p53 binds and destabilizes HIF- 1α 435,483,487–489,492,498–502 . p53 also represses HIF-1-dependent transcription at some genes, including VEGF and metabolic genes such as carbonic anhydrase IX 435,483,500,501,503–507 . Repression may be through direct binding or through competition between p53 and HIF-1 for coactivators such as p300 492,503 .…”

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

“…p53 increases expression of collagen prolyl hydroxylase expression, and increases the anti-angiogenic collagen fragment endostatin 511 . Thus p53 serves as an inhibitor of angiogenesis and metabolic changes during cancer progression 435,508 . Interestingly, there is selection pressure to inactivate p53 in tumor stroma, perhaps to promote angiogenesis 435 .…”

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

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The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

Woodby

Scott

Bodily

2016

Progress in Molecular Biology and Translational Science

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Human papillomaviruses (HPV) are small, double-stranded DNA viruses that replicate in stratified squamous epithelia and cause a variety of malignancies. Current efforts in HPV biology are focused on understanding the virus-host interactions that enable HPV to persist for years or decades in the tissue. The importance of interactions between tumor cells and the stromal microenvironment has become increasingly apparent in recent years, but how stromal interactions impact the normal, benign life cycle of HPVs or progression of lesions to cancer is less understood. Furthermore, how productively replicating HPV impacts cells in the stromal environment is also unclear. Here we bring together some of the relevant literature on keratinocyte-stromal interactions and their impacts on HPV biology. We discuss how HPV oncogenes in infected cells manipulate other cells in their environment, and, conversely, how neighboring cells may impact the efficiency or course of HPV infection.

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Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

Section: Angiogenesis and The Hypoxic Responsementioning

confidence: 99%

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The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

Woodby

Scott

Bodily

2016

Progress in Molecular Biology and Translational Science

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p53 mutations define the chromatin landscape to confer drug tolerance in pancreatic cancer

et al. 2022

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Somatic inactivation of p53 (TP53) mainly occurs as missense mutations that lead to the acquisition of neomorphic mutant protein forms. p53 mutants have been postulated to exert gain-of-function (GOF) effects, including promotion of metastasis and drug tolerance, which generally contribute to the acquisition of the lethal phenotype. Here, by integrating a p53 R270H -dependent transcriptomic analysis with chromatin accessibility (ATAC-seq) profiling, we shed light on the molecular basis of a p53 mutant-dependent drug-tolerant phenotype in pancreatic cancer. p53 R270H finely tunes chromatin accessibility in specific genomic loci, orchestrating a transcriptional programme that participates in phenotypic evolution of the cancer. We specifically focused on the p53 R270H -dependent regulation of the tyrosine kinase receptor macrophage-stimulating protein receptor (MST1r). MST1r deregulation substantially impinged on drug response in the experimental model, recapitulating the p53 R270H -dependent phenotype, and strongly correlated with p53 mutant and aggressive phenotype in pancreatic cancer patients. As cellular plasticity in the final stages of the evolution of pancreatic cancer seems to predominantly originate from epigenetic mechanisms, we propose that mutant p53 participates in the acquisition of a lethal phenotype by fine-tuning the chromatin landscape.

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The heterogeneous impact of targeted therapy on the prognosis of stage III/IV colorectal cancer patients with different subtypes of TP53 mutations

Chen,

Chang,

et al. 2023

Cancer Medicine

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BackgroundThe relationship between molecular characteristics and the prognosis of colorectal cancer (CRC) patients has not been fully understood. This study explored the impact of targeted therapy on the prognosis of CRC patients with different TP53 mutations, in the context of comprehensive treatment.MethodsThis study included patients with stage III/IV primary CRC from the electronic medical record system. TP53 mutations were detected via next‐generation sequencing (NGS) using formalin‐fixed paraffin‐embedded (FFPE) tissues. Applying two methods, we classified TP53 mutations as gain of function (GOF)/non‐GOF mutations or known/likely loss of function (LOF) mutations. Kaplan–Meier plot and parametric survival analysis were performed to evaluate the prognosis of CRC patients and identify potential predictors.ResultsThere were 286 patients included, of which 166 (58.04%) patients received targeted therapy and 120 (41.96%) did not. There were 286 patients in the TP53 GOF classification set and 247 in the TP53 LOF classification set. Parametric survival analysis, adjusted for sex, onset, KRAS mutation, sidedness, stage, and surgery, showed that receiving targeted therapy predicted better overall survival (OS) among patients who harbored TP53 GOF mutations (HR 0.40, 95% confidence interval (CI) [0.21, 0.76], p = 0.005) or known LOF mutations (HR 0.21, 95% CI [0.07, 0.60], p = 0.002). However, there was no significant impact of receiving targeted therapy on OS among patients harboring TP53 non‐GOF mutations (HR 1.68, 95% CI [0.50, 5.63], p = 0.403) or likely LOF mutations (HR 0.90, 95% CI [0.34, 2.39], p = 0.837).ConclusionsReceiving targeted therapy had a heterogeneous impact on the prognosis of CRC patients harboring different TP53 mutations. These results provide promising value for future personalized treatment and precision medicine.

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The p53 family and the hypoxia-inducible factors (HIFs): determinants of cancer progression

Cited by 128 publications

References 102 publications

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

The Interaction Between Human Papillomaviruses and the Stromal Microenvironment

p53 mutations define the chromatin landscape to confer drug tolerance in pancreatic cancer

The heterogeneous impact of targeted therapy on the prognosis of stage III/IV colorectal cancer patients with different subtypes of TP53 mutations

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