Fig. 3.

Different p53 mutations and their potential effects on its function and oncogenic activity. Mutation of TP53 genes is associated with inactivation of wild-type TP53 gene and 75% of P53 mutations lead to loss of p53 functions. Inactivation of the wild type function of p53 promotes invasion, proliferation, cell survival, cancer progression, and metastasis. The effects of p53 mutations are mediated by interaction with key molecular pathways that includes: Inhibition of mTor kinase, inhibition of Cip1, NF-κB activation, stimulation of Raf/MEK/ERK cascade, inhibition of p53/p21/p27 and p53/Bcl-2/Bax pathways, inhibition of ITIH5 tumour suppressor gene, activation of ZEB1 and ZEB2 transcription factors and induction of epithelial–mesenchymal transition. Ablation of R248Q p53 mutation in CRC inhibits STAT3-mediated tumor growth and invasion. The net effects of p53 mutations is the loss of the protective effects of wild p53 proteins which lead to cancer progression