IGF2 and neoplasm: In this study, we demonstrated that 1) β-AR mediates NNK-induced IGF-1R activation through the up-regulation of IGF2 transcription; 2) the Gβγ subunits dissociated from β-AR upon NNK exposure stimulate IGF-1R through the PLC-mediated pathway; and 3) the inhibition of β-AR suppresses NNK-mediated malignant cell transformation and tumor formation in mice.