Tumour-associated p53 missense mutants act as driver oncogenes affecting cancer progression, metastatic potential and drug resistance (gain-of-function) <sup>1</sup> .
These mutations include p53-inactivating mutations as well as oncogenic gain-of-function (GOF) mutations that endow p53 with capabilities to promote tumor progression.
To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression.
The high expression of p19<sup>ARF</sup> correlated with mutant p53 accumulation and tumor progression, suggesting a dual role of p19<sup>ARF</sup> in tumor promotion or suppression that might depend on the p53 mutation status in tumor cells.
In mice, we demonstrated that combined inactivation of Mir34a and Tp53 promotes azoxymethane-induced colorectal carcinogenesis and tumor progression and metastasis by increasing levels of IL6R and PAI1.
Although its standard functions are strongly connected to tumor suppression, p53 mutants and aggregates are involved in cancer progression. p53 aggregates are heterogeneous assemblies composed of amorphous aggregates, oligomers, and amyloid-like fibrils.
ROR is one of large intergenic non-coding RNAs (lincRNAs) and acts as a strong negative regulator of p53 and a sponge for miR-145 to regulate diverse cancer progression.
However, Arf loss and p53 loss produce differing outcomes-loss of p53 promotes both tumor initiation and progression; loss of Arf promotes tumor progression but not initiation.
In the overall series of cases, p53 overexpression was associated with tumor progression (hazard ratio [HR]=3.18, 95% confidence interval [CI] 1.19-8.48, P=.02), but this association was even stronger if having any alteration in any of the 2 genes was considered (HR=3.51, 95% CI 1.34-9.21, P=.01).
However, whether the state of p53 in MSCs can impact the bioactive molecule secretion of exosomes to promote cancer progression and the regulatory mechanism remains elusive.
Finally, we discuss the functional role of the interplay between mutant p53 proteins and autophagy in cancer progression, a fundamental knowledge to design more effective therapies against cancers bearing mutant TP53 gene.
Collectively, these data show that ROCK2 activation induces malignancy in ras<sup>Ha</sup>-initiated/promoted papillomas in the context of p53 loss and novel NF-κB expression, whereas increased tissue rigidity and cell motility/contractility help mediate tumour progression.
The lag period between induction of total PP or PP/Trp53 KO and melanoma development indicates that additional genetic or epigenetic alterations may account for neoplastic progression.
Our results first demonstrate that p53 enables Oligo-Fucoidan to effectively inhibit tumor progression, and Oligo-Fucoidan minimizes the side effects of chemotherapy and alters tumor microenvironment.
Our results show that synergism between ERβ and p53 inactivation functions to determine important aspects of breast oncogenesis and cancer progression.
TP53 is highly mutated in ESCC, and missense mutations are associated with poor overall survival, independently of pathological stage, suggesting that these missense mutations have important functional impacts on tumour progression, and are thus likely to be gain-of-function (GOF) mutations.