TGFB1 and neoplasm: Meanwhile, structural mutations destabilize the p53 structure and reduce its thermostability which can lead to misfolding and again lack of DNA binding, this includes residues R175H, G245S, Y220C and R249S.151 Due to these types of mutations, p53 can now bind to and inhibit tumor suppressors (e.g. p63, p73)152 and enhance survival and proliferation.151 This newfound GOF activity can increase genomic instability, resistance to pro-apoptotic signals and drug resistance, tumor aggressiveness, metastatic potential and can promote TGF-β pro-tumourigenic properties.153