α-SMA-Cre-mediated excision of PDK1 reveals an essential role of PDK1 in regulating morphology of cardiomyocyte and tumor progression in tissue microenvironment.

ABSTRACT

The phosphoinositide-3 kinase (PI3K) - phosphoinositide-dependent protein kinase 1 (PDK1)-Akt/protein kinase B (PKB) cascade plays a critical role in cardiovascular development and tumor genesis. But the role of PDK1 in the microenvironment of heart and tumor remains unknown. To clarify the effects of PDK1 on tissue microenvironment in vivo, here, we created α-SMA-Cre-mediated excision of PDK1 mice. And the mice were injected subcutaneously with Lewis lung carcinoma (LLC) cells. We found PDK1-deficient mice had post-natal praecox dilated cardiomyopathy, decelerated tumor growth and severe tumor metastasis. Histopathological analysis revealed abnormality of vascular microenvironment in heart and primary tumor. In conclusion, PDK1 plays a pivotal role in regulating cardiac function and tumor metastasis by interfering with microenvironment.