We found that forced over-expression of p53-R175H significantly promoted cell migration and invasion, and induced activation of the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/AKT pathway.
We have performed laser capture microdissection with RNA microarray analysis on the invasive and non-invasive tumor cells of p53(R175H)-overexpressing OTC samples to determine candidate genes facilitating tumor invasion.
Using the SKBR3 breast cancer and p53-null H1299 lung cancer cells stably expressing the R175H p53 mutant protein, we demonstrated that GON triggers the appearance of a wild-type-like p53 protein by using conformation-specific antibodies, immunoprecipitation, DNA-binding assays and target gene expression. p53 restoration was associated with a G2/M arrest, senescence, reduced cell migration, invasion and increased cell death.
Using esophageal epithelial cells transformed by the overexpression of EGFR and p53(R175H), we find novel evidence of a functional link between p53(R175H) and the c-Met receptor tyrosine kinase to mediate tumor cell invasion.