磷酸肌醇-3激酶(PI3K)-磷酸肌醇依赖性蛋白激酶1(PDK1)-Akt/蛋白激酶B(PKB)级联在心血管发育和肿瘤发生中起关键作用。但是PDK1在心脏和肿瘤微环境中的作用仍然未知。为了阐明PDK1对体内组织微环境的影响,在这里,我们创建了α-SMA-Cre介导的PDK1小鼠切除术。小鼠皮下注射Lewis肺癌(LLC)细胞。我们发现缺乏PDK1的小鼠有出生后praecox扩张型心肌病,减缓肿瘤生长和严重的肿瘤转移。组织病理学分析显示心脏和原发肿瘤血管微环境异常。总之,PDK1通过干扰微环境在调节心脏功能和肿瘤转移中起关键作用。
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.