PIK3CA and cancer: This study shows that the PI3K-Akt pathway promotes cell proliferation via the Yorkie/YAP transcriptional coactivator in response to mechanical stretching in vivo; the Hippo kinase acts as a key integrator of Akt and mechanical cues to control Yorkie/YAP activity and cell proliferation, with implications for human cancer, in which PI3K-Akt and mechanical forces play key roles in driving cell proliferation and malignancy.