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Full-Text Articles in Medicine and Health Sciences
Tgfβ/Smad3 Regulates Proliferation And Apoptosis Through Irs-1 Inhibition In Colon Cancer Cells., Katie L. Bailey, Ekta Agarwal, Sanjib Chowdhury, Jiangtao Luo, Michael G. Brattain, Jennifer D. Black, J. Wang
Tgfβ/Smad3 Regulates Proliferation And Apoptosis Through Irs-1 Inhibition In Colon Cancer Cells., Katie L. Bailey, Ekta Agarwal, Sanjib Chowdhury, Jiangtao Luo, Michael G. Brattain, Jennifer D. Black, J. Wang
Journal Articles: Eppley Institute
In this study, we have uncovered a novel crosstalk between TGFβ and IGF-1R signaling pathways. We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFβ/Smad3 signaling. Loss or attenuation of TGFβ activation leads to elevated expression and phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell proliferation, decreased apoptosis and increased tumor growth in vitro and in vivo. Downregulation of IRS-1 expression reversed Smad3 knockdown-mediated oncogenic phenotypes, indicating that TGFβ/Smad3 signaling inhibits cell proliferation and increases apoptosis at least partially through the inhibition of IRS-1 expression and activation. …
Co-Targeting Hgf/Cmet Signaling With Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Vivian Chua, Connie Liao, Timothy J. Purwin, Mizue Terai, Ken Kageyama, Michael A. Davies, Takami Sato, Andrew E. Aplin
Co-Targeting Hgf/Cmet Signaling With Mek Inhibitors In Metastatic Uveal Melanoma., Hanyin Cheng, Vivian Chua, Connie Liao, Timothy J. Purwin, Mizue Terai, Ken Kageyama, Michael A. Davies, Takami Sato, Andrew E. Aplin
Department of Cancer Biology Faculty Papers
Patients with metastatic uveal melanoma usually die within 1 year of diagnosis, emphasizing an urgent need to develop new treatment strategies. The liver is the most common site of metastasis. Mitogen-activated protein kinase kinase (MEK) inhibitors improve survival in V600 BRAF-mutated cutaneous melanoma patients but have limited efficacy in patients with uveal melanoma. Our previous work showed that hepatocyte growth factor (HGF) signaling elicits resistance to MEK inhibitors in metastatic uveal melanoma. In this study, we demonstrate that expression of two BH3-only family proteins, Bim-EL and Bmf, contributes to HGF-mediated resistance to MEK inhibitors. Targeting HGF/cMET signaling with LY2875358, a …