The findings of the present study indicated that PEDF may trigger autophagy in HUVECs by inducing p53 and sestrin2 expression, and inhibiting mTOR expression; these findings may contribute to the improved understanding of diseases, including cancer and atherosclerosis.
Numerous cellular and animal model studies indicate that an unbalance in p53 isoform expression in specific cell types causes age-related disorders such as cancer, premature ageing, and degenerative diseases.
For example, ectopic expression of microRNA-34a (miR-34a), a tumor suppressor gene that is a direct transcriptional target of p53 and thus is reduced in p53 mutant tumors, has clear effects on cell proliferation and survival in murine models of cancer.
One such small molecule drug Nutlin binds the protein MDM2, which is upregulated in several types of cancer and is a negative regulator of the tumor suppressor protein p53.
Our results show that farnesylated DNAJA1 is a crucial chaperone in maintaining mutant p53 stabilization and targeting farnesylated DNAJA1 by atorvastatin will be critical for inhibiting p53 mutant cancer.
Subsequently, 7,893 cancer cases were compiled in cBioPortal for Cancer Genomics from the 33 most recent The Cancer Genome Atlas (TCGA) studies to determine the prevalence of TP53 mutations in cancers and their effects on survival and disease-free survival times.
Bortezomib inhibited the growth of intestinal adenomas and xenograft tumors with wild-type p53, indicating the importance of p53 in the response to proteasome inhibitors in tissue homeostasis and in cancer therapy.
Because of the diversity of human cancers with p53 mutations, these findings raise important questions whether this mechanism operates in different cancer types with same or different p53 mutations.
Area covered: Here, we summarise the p53 isoforms and their relevance to cancer to establish an understanding and theorise on potential applications of the isoforms in clinical practice.
Surprisingly, the antiproliferative activity of C-2 substituted cambinol derivatives was not correlated to the induction of p53 protein, as evaluated by the analysis of the cell viability on wild-type and p53 mutated cancer cell lines, and further confirmed by western blot analyses.
Germline DNA from 1054 BRCA-mutation-negative Hispanic women with hereditary BC (BC diagnosed at age <51 years, bilateral BC, breast and ovarian cancer, or BC diagnosed at ages 51-70 years with ≥2 first-degree or second-degree relatives who had BC diagnosed at age <70 years), 312 local controls, and 887 multiethnic cohort controls was sequenced and analyzed for 12 known and suspected, high-penetrance and moderate-penetrance cancer susceptibility genes (ataxia telangiectasia mutated [ATM], breast cancer 1 interacting protein C-terminal helicase 1 [BRIP1], cadherin 1 [CDH1], checkpoint kinase 2 [CHEK2], nibrin [NBN], neurofibromatosis type 1 [NF1], partner and localizer of BRCA2 [PALB2], phosphatase and tensin homolog [PTEN], RAD51 paralog 3 [RAD51C], RAD51D, serine/threonine kinase 11 [STK11], and TP53).
Here we report that miR-520d-5p (520d-5p) causes undifferentiated cancer cells to adopt benign or normal status in vivo in immunodeficient mice via demethylation and P53 upregulation.
GSK-3 is the central hub that orchestrates signals from the Wnt/β-catenin, PI3K/PTEN/Akt/mTOR, Ras/Raf/MEK/ERK, hedgehog, Notch and TP53 pathways to elicit regulatory influences on cancer initiation, epithelial-mesenchymal transition, and resistance to therapy.
In contrast to the notion that Hsp90 interacts with and protects mutant p53 in cancer, Hsp90β preferentially bound to wild-type p53 and modulated its degradation via a proteasome-dependent manner.
Reports of variable cancer penetrance in Li-Fraumeni syndrome (LFS) have raised questions regarding the prevalence of pathogenic germline TP53 variants.
It is expected that the results of this research would be helpful to better understand the biological functions of p53 pathway and provide some clues in the treatment of cancer.