Upon IGF-1 stimulation, pVHL-deficient RCC cells exhibit high rate of RACK1/IGF-IR binding and up-regulated IGF-1R tyrosine kinase activity, phosphoinositide 3-kinase/serine-threonine kinase Akt (PI3K/Akt) signaling and matrix metalloproteinase-2 (MMP-2) activity and high cellular invasiveness [95]. Here, VHL is linked to renal cell carcinoma.