title: 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.
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China; Department of Pneumology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China.
authors.forename: X-J
authors.initials: XJ
authors.lastname: Qian
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
authors.forename: X-L
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pneumology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China.
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China. Electronic address: fengqiuting1@163.com.
authors.forename: Q-T
authors.initials: QT
authors.lastname: Feng
authors.affiliation: Department of Cardiology, Affiliated Hospital of Nanjing Medical University, Wuxi No. 2 People's Hospital, Wuxi, Jiangsu 214002, PR China.
authors.forename: C-J
authors.initials: CJ
authors.lastname: Yang
mesh_terms: D000199:Actins / Q000235:genetics; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics / Q000473:pathology; D048430:Cell Shape / Q000235:genetics; D018450:Disease Progression; D005260:Female; D017353:Gene Deletion; D055786:Gene Knockout Techniques; D019426:Integrases / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology* / Q000502:physiology; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D000199:Actins; C000631433:Pdk1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; C544013:alpha-smooth muscle actin, mouse; D017346:Protein Serine-Threonine Kinases; C045073:Cre recombinase; D019426:Integrases
keywords: Dilatation cardiaque; Heart failure; Knock-out mice; Microenvironment; Microenvironnement; PDK1; Souris knock-out; Tumeur; Tumor