Role of p53 in breast cancer progression: An insight into p53 targeted therapy

Marvalim, Charlie; Datta, Arpita; Lee, Soo‐Chin

doi:10.7150/thno.81847

Cited by 35 publications

(29 citation statements)

References 201 publications

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“…Mutant p53 also can increase expression of chromatin-regulated genes which related to enhanced histone acetylation and methylation and contributes to BC progression [25]. Also, elevated mutant p53 levels are associated with many events that related to poor clinical outcomes and increased BC metastasis and invasion [22] including evading apoptosis [26] and activation of the transcription of many genes related to cell proliferation [27].…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C virus may accelerate breast cancer progression by increasing mutant p53 and c-Myc oncoproteins circulating levels

Fathy

Abdelrazek

Attallah

et al. 2023

Preprint

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Background: Hepatitis C virus (HCV) was reported to relate to polymorphous and frequent extrahepatic manifestation. Despite the limited studies, HCV viral oncoproteins may be implicated in breast cancer (BC) tumor aggressiveness. In a trial to elucidate a mechanistic link, this study aimed to investigate a mutant p53 and c-Myc oncoproteins expression levels in BC patients with and without HCV infection. Methods: A total of 215 BC patients (119 infected and 96 non-infected with HCV) were collected. ELISA was used for detection of anti-HCV antibodies, mutant p53, c-Myc, HCV-NS4, CEA, CA 125 and CA-15.3. Results: HCV infection was related to BC late stages, lymph node invasion, distant metastasis, high grades and large size. HCV infected patients had a significantly (P<0.05) higher WBCs, ALT and AST activity, bilirubin CEA, CA125 and CA15.3 levels, and reduced haemoglobin, albumin and RBCs count. Regardless of tumor severity, HCV infection was associated with significant elevated levels of mutant p53 (22.5±3.5 µg/mL; 1.9-fold increase) and c-Myc (21.4±1.8 µg/mL; 1.5-fold increase). Among HCV-infected patients, elevated levels of p53 and c-Myc were significantly correlated with elevated tumor markers (CEA, CA 125 and CA15.3) and HCV-NS4 levels. Conclusions: this study concluded that HCV infection may be accompanied with BC severity behaviour and this may be owing to elevated expression of mutant p53 and c-Myc oncoproteins.

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Section: Discussionmentioning

confidence: 99%

Hepatitis C virus may accelerate breast cancer progression by increasing mutant p53 and c-Myc oncoproteins circulating levels

Fathy

Abdelrazek

Attallah

et al. 2023

Preprint

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“…Therefore, the target gene FOSL1 of mutant p53 may be a promising therapeutic target for invasive tumors. The transcription function of mutp53 is mainly dependent on its synergistic effects with other transcription factors, disrupting or enhancing its target genes by binding to other transcription factors [3]. The optimal transcription function of mutant p53 is interacting with other TFs to regulate target gene expression jointly [5,31].…”

Section: Discussionmentioning

confidence: 99%

“…Mutant p53 (mutp53) has been found in over half of all types of human cancers, making it a potential target for tumor therapy [2]. One strategy is to reactivate the wild-type function in mutp53, which has proven challenging to implement in practice because activating the role of proteins is much more complicated than pharmacologically inhibiting them [3]. Alternatively, targeting the downstream of mutp53 may be a more readily available approach.…”

mentioning

confidence: 99%

Mutant p53 and ELK1 co‐drive FRA‐1 expression to induce metastasis in breast cancer

Hu,

Wang,

et al. 2023

FEBS Letters

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Tumor‐associated p53 mutations induce activities different from wild‐type p53, thus causing loss of the protein's tumor inhibition function. The cells carrying p53 mutations have more aggressive characteristics related to invasion, metastasis, proliferation, and cell survival. By comparing the gene expression profiles of mutant p53 (mutp53) and mutp53 silenced cohorts, we found that FOS‐related antigen‐1 (FRA‐1), which is encoded by FOSL1, is a potential effector of mutp53‐mediated metastasis. We demonstrate that the expression of FRA‐1, a gatekeeper of mesenchymal–epithelial transition, is elevated in the presence of p53 mutations. Mechanistically, mutant p53 cooperates with the transcription factor ELK1 in binding and activating the promoter of FOSL1, thus fostering lung metastasis. This study reveals new insights into how mutant p53 contributes to metastasis in breast cancer.

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“…40 It was found that Bcl-2 family proteins are significantly associated with the AKT/mTOR signalling pathway. 41 Furthermore, HHT could up-regulate the tumour suppressor P53, 42 the pro-apoptotic factor Bax, 43…”

Section: Discussionmentioning

confidence: 99%

Homoharringtonine induces apoptosis of mammary carcinoma cells by inhibiting the AKT/mTOR signaling pathway

Zhang,

Mei,

Liang

et al. 2023

Vet Comparative Oncology

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Mammary tumour is the most common type of tumour in dogs, especially in unneutered female dogs. Homoharringtonine (HHT) is a natural alkaloid that can be used to treat various types of human tumour. However, the inhibitory effect and mechanism of HHT on canine mammary carcinomas (CMC) remain unclear. This study aimed to evaluate the inhibitory effect of HHT on CMC in vitro and determine its underlying molecular mechanism. The effects of HHT on the cytotoxicity of CMC U27 cells were evaluated by the cell counting kit‐8, wound healing, and Transwell assays. HHT‐induced apoptosis of U27 cells was detected by JC‐1 and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay. Moreover, the gene expression of B‐cell lymphoma‐2 (Bcl‐2) and Bcl‐2 associated X protein (Bax) were analysed using quantitative reverse transcription‐polymerase chain reaction (RT‐qPCR), and the protein expression of protein kinase B/mammalian target of rapamycin (AKT/mTOR) and mitochondrial apoptosis proteins were determined by western blotting. Furthermore, mammary tumour‐bearing mouse models were established using 4T1 cells to evaluate the therapeutic effect of HHT. It was found that HHT could significantly down‐regulated the protein expression of p‐AKT, p‐mTOR, and Bcl‐2, and up‐regulated the protein expression of P53, Bax, cleaved caspase‐3, and cleaved caspase‐9. In addition, HHT significantly suppressed both tumour volume and mass in mammary tumour mice. In conclusion, HHT damages CMC cells by inhibiting the AKT/mTOR signalling pathway and inducing mitochondrial apoptosis. Such findings lay a theoretical foundation for the clinical treatment of CMC and provide more options for clinical medication.

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Role of p53 in breast cancer progression: An insight into p53 targeted therapy

Cited by 35 publications

References 201 publications

Hepatitis C virus may accelerate breast cancer progression by increasing mutant p53 and c-Myc oncoproteins circulating levels

Hepatitis C virus may accelerate breast cancer progression by increasing mutant p53 and c-Myc oncoproteins circulating levels

Mutant p53 and ELK1 co‐drive FRA‐1 expression to induce metastasis in breast cancer

Homoharringtonine induces apoptosis of mammary carcinoma cells by inhibiting the AKT/mTOR signaling pathway

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