Blobe Lab
Tel: (919) 668-1352
Email: blobe001@mc.duke.edu
Role of TGF-beta in Human Malignancy In normal, non-transformed cells, the TGF-beta ligand acting through the TGF-beta signalling pathway induces G1 cell cycle arrest to inhibit proliferation, induce differentiation, or promote apoptosis. During transformation into cancerous cells, various components of the TGF-beta signaling pathway are mutated, making the cancer cells resistant to the effects of the TGF-beta ligand. These TGF-beta resistant cancer cells, which proliferate in an unregulated manner, as well as the surrounding stromal cells (fibroblasts) then increase their production of the TGF-beta ligand. This TGF-beta, by acting on the surrounding stromal cells, immune cells, and endothelial and smooth muscle cells, results in enhanced immunosuppression and angiogenesis, as well as increased invasiveness of the tumor, allowing for enhanced tumor invasion and metastasis.
Selected Publications: [All Publications]
Chen, W, Kirkbride, K.C., How, T., Nelson, CD, Mo, J., Frederick, JP, Wang, X-F., Lefkowitz, R.J. and Blobe, G.C. b-Arrestin 2 Mediates Internalization of the Type III TGF-b Receptor and Down Regulation of its Signaling. Science 2003; 301:1394-1397. [Full Text] [Related Perspective]
Elliott, R.L. and Blobe, G.C. Role of Transforming Growth Factor b in Human Cancer. J Clin Oncol 2005; 23:2078-2093. [Full Text]
Dong, M., How, T., Kirkbride, K.C., Gordon, K.G., Lee, J.D., Hempel, N., Kelly, P., Moeller, B.J., Hempel, N., Marks, J.R. and Blobe, G.C. The type III TGF-b receptor suppresses breast cancer progression. J. Clin. Inv. 2007; 117:206-17. [Full Text]
Turley, R.S., Finger, E.C., Hempel, N., Fields, T.A. and Blobe, G.C. The type III TGF-b Receptor as a Novel Tumor Suppressor Gene in Prostate Cancer. Cancer Research 2007; 67:1090-1098. [Full Text]
Hempel, N., How, T., Dong, M., Murphy, S.K., Fields, T. and Blobe, G.C. Loss of Betaglycan expression in Ovarian Cancer: Role in Motility and Invasion Cancer Research Cancer Research 2007; 67:5231-8. [Full Text]
Lee, N.Y., and Blobe, G.C. The Interaction of Endoglin with b-arrestin2 Regulates Transforming Growth Factor-b-mediated ERK Activation and Migration in Endothelial Cells J Biol Chem 2007; 282: 21507-21517. [Full Text]
You, H.J., Bruinsma, M.W., How, T., Ostrander, J.H. and Blobe, G.C. The type III TGF-b Receptor Signals through both Smad3 and the p38 MAP Kinase Pathways to Contribute to Inhibition of Cell Proliferation. Carcinogenesis 2007; 28:2491-2500.[Full Text]
Kirkbride, K.C., Townsend, T.A., Bruinsma, M.W., Barnett, J.V. and Blobe, G.C. Bone Morphogenetic Proteins signal through the Transforming Growth Factor-b Type III receptor. J Biol Chem; 2008: 283: 7628-7637. [Full Text]
Web Sites:
COS Profile: http://myprofile.cos.com/gblobe
Article in Inside Duke: http://inside.duke.edu/article.php?IssueID=74&ParentID=5271
Affiliations of the Blobe Lab:
Duke University Medical Center
Department of Medicine/ Division of Medical Oncology
Department of Pharmacology and Cancer Biology
University Program in Cell and Molecular Biology
University Program in Molecular Cancer Biology
TGF-beta Signaling Links
Massague Overview in Nature MCB Reviews
Moustakas Lab-Ludwig Institute for Cancer Research
Schiemann Lab at University of Colorado Health Sciences Center, Denver
TGF-beta Meetings