title: TGFβ signaling in pancreatic ductal adenocarcinoma.
abstract: Transforming growth factor β (TGFβ) receptor signaling plays a paradoxical effect in the tumorigenesis of pancreatic ductal adenocarcinoma (PDAC), in which its tumor-inhibitory role at early stages turns into a tumor-promoting role at later stages. The underlying mechanism remains far from clear. Here we provide strong evidence that the activation of TGFβ receptor signaling in PDAC cells increased SMAD3 phosphorylation and nuclear translocation to inhibit cell growth. Meanwhile, it also activated SMAD7 to induce nuclear translocation and retention of β-catenin, which not only attenuated the inhibition of cell growth by nuclear SMAD3 but also activated vascular endothelial growth factor A (VEGF-A) to promote vascularization. Our data thus support a model involving crosstalk of the TGFβ and Wnt signaling pathways, for regulating the complicated effect of TGFβ signaling on the tumorigenesis of PDAC.
authors.affiliation: Department of Hepatobiliary Surgery, Air Force General Hospital of PLA, 30 Fucheng Road, Beijing, 100142, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Chengli
authors.initials: C
authors.lastname: Liu
authors.forename: Yalin
authors.initials: Y
authors.lastname: Kong
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
mesh_terms: D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D015398:Signal Transduction; D051900:Smad3 Protein / Q000378:metabolism; D051906:Smad7 Protein / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: C497806:SMAD7 protein, human; D051900:Smad3 Protein; D051906:Smad7 Protein; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D051176:beta Catenin