Hsp90 is also required for induction of vascular endothelial growth factor (VEGF) and nitric oxide synthase (NOS). Both are important for "de novo" angiogenesis that is required for tumour growth beyond the limit of diffusion distance of oxygen in tissues. It also promotes the invasion step of metastasis by assisting the matrix metalloproteinase MMP2. Together with its co-chaperones, Hsp90 modulates tumour cell apoptosis "mediated through effects on AKT, tumor necrosis factor receptors (TNFR) and nuclear factor-κB (NF-κB) function." Also, Hsp90 participates in many key processes in oncogenesis such as self-sufficiency in growth signals, stabilization of mutant proteins, angiogenesis, and metastasis.