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New Stuff

In addition to direct interruption of intracellular signaling network, tumour cells have altered production of, and/or responsiveness to, stimulatory or inhibitory growth and differentiation factors. Among these, transforming growth factor beta (TGF-ß) and its cell surface receptors and intracellular signaling molecules are key determinants in cancer development. TGF-ß can act both as a tumour suppressor during early stages of normal to cancer transformation and as a stimulator during late stages of tumour progression in invasion and metastasis. To understand its tumor suppressive effects, we have established cellular and animal models in which various biological functions are dissected and are identifying specific signaling pathways responsible for particular biological functions. We have also created tumour models in which TGF-ß stimulates epithelial to mesenchymal transition and tumour invasion. In particular we are focusing on the differential cooperation between various mitogen activated protein kinases (MAPK) and TGF-ß signaling pathways and on the integration of the oncogene Ras and TGF-beta pathways in tumour invasion and metastasis.

Lab members involved in the research:

• Hong-Jian Zhu
• Kaye Stenvers
• Melinda Tursky
• Josie Iaria
• Kellie Cartledge
• Bo Wang

Publications:

Heart and Liver Defects and Reduced Transforming Growth Factor-ࢸ Sensitivity in Transforming Growth Factor-ß Type III Receptor-Deficient Embryos
Stenvers KL, Tursky ML, Kountouri N, Amatayakul-Chantler S, Grail D, Small C, Weinberg RA, Sizeland AM, Zhu H-J
Submitted

Smad7 inhibits fibrotic effect of tgf-Beta on renal tubular epithelial cells by blocking smad2 activation.
Li JH, Zhu HJ, Huang XR, Lai KN, Johnson RJ, Lan HY.
J Am Soc Nephrol. 13: 1464-1472 (2002). [Medline entry]

Regulation of Transforming Growth Factor-beta Signaling.
Zhu HJ, Burgess AW.
Mol Cell Biol Res Commun. 4: 321-330 (2001). [Medline entry]

Smad7 differentially regulates transforming growth factor beta-mediated signaling pathways.
Zhu HJ, Iaria J, Sizeland AM.
J Biol Chem. 274:32258-32264 (1999). [Medline entry]

Extracellular domain of the transforming growth factor-beta receptor negatively regulates ligand-independent receptor activation.
Zhu HJ, Sizeland AM.
J Biol Chem. 274:29220-29227 (1999). [Medline entry]

A pivotal role for the transmembrane domain in transforming growth factor-beta receptor activation.
Zhu HJ, Sizeland AM.
J Biol Chem. 274:11773-11781 (1999). [Medline entry]