Figure 7. A feedback loop mediated by the PI3K-Akt axis controls Grb7 expression.

Grb7 interacts with HER2, participates in HER2 signaling, and promotes cell survival and cell migration. HER2 exerts a repressive control on Grb7 via the PI3K-Akt pathway. Inhibition of HER2 signaling (e.g. by lapatinib) de-represses Grb7 causing its rapid upregulation. Reducing Grb7 with RNAi or preventing its interaction with HER2 using protein-protein interaction inhibitors may help increase the efficacy of anti-HER2 therapeutics and avoid the adverse consequences of Grb7 oncogenic activity.