STAT3 and cancer: It is well known that signal transducer and activator of transcription 3 (Stat3) activation plays a key role in polarization of M2 macrophage,33 and PYK2 forms a positive feedback loop with Stat3 to promote cancer metastasis.34 Indeed, activation of Stat3, but not Stat5, and cell migration were significantly increased in Raw246.7 cells treated with Rab22a-NeoF1-exo compared to those treated by Vector-exo (Fig. 6b and Supplementary Fig. 6d), and such increases were abolished when Raw246.7 cells were treated with either Rab22a-NeoF1-shPYK2#1-exo or Rab22a-NeoF1-shPYK2#2-exo.