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Articles 1 - 3 of 3
Full-Text Articles in Biochemistry, Biophysics, and Structural Biology
Twist-Mediated Epithelial-Mesenchymal Transition Promotes Breast Tumor Cell Invasion Via Inhibition Of Hippo Pathway, Yifan Wang, Jingyi Liu, Xuhua Ying, Pengnian Charles Lin, Binhua P. Zhou
Twist-Mediated Epithelial-Mesenchymal Transition Promotes Breast Tumor Cell Invasion Via Inhibition Of Hippo Pathway, Yifan Wang, Jingyi Liu, Xuhua Ying, Pengnian Charles Lin, Binhua P. Zhou
Molecular and Cellular Biochemistry Faculty Publications
Twist is a key transcription factor for Epithelial-mesenchymal transition (EMT), which is a cellular de-differentiation program that promotes invasion and metastasis, confers tumor cells with cancer stem cell (CSC)-like characteristics, and increases therapeutic resistance. However, the mechanisms that facilitate the functions of Twist remain unclear. Here we report that Twist overexpression increased expression of PAR1, an upstream regulator of the Hippo pathway; PAR1 promotes invasion, migration, and CSC-like properties in breast cancer by activating the transcriptional co-activator TAZ. Our study indicates that Hippo pathway inhibition is required for the increased migratory and invasiveness ability of breast cancer cells in Twist-mediated …
P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A Brekken, Craig W. Vander Kooi, Arthur M. Mercurio
P-Rex1 Promotes Resistance To Vegf/Vegfr-Targeted Therapy In Prostate Cancer, Hira Lal Goel, Bryan Pursell, Leonard D. Shultz, Dale L. Greiner, Rolf A Brekken, Craig W. Vander Kooi, Arthur M. Mercurio
Molecular and Cellular Biochemistry Faculty Publications
Autocrine VEGF signaling is critical for sustaining prostate and other cancer stem cells (CSCs), and it is a potential therapeutic target, but we observed that CSCs isolated from prostate tumors are resistant to anti-VEGF (bevacizumab) and anti-VEGFR (sunitinib) therapy. Intriguingly, resistance is mediated by VEGF/neuropilin signaling, which is not inhibited by bevacizumab and sunitinib, and it involves the induction of P-Rex1, a Rac GEF, and consequent Rac1-mediated ERK activation. This induction of P-Rex1 is dependent on Myc. CSCs isolated from the PTENpc−/− transgenic model of prostate cancer exhibit Rac1-dependent resistance to bevacizumab. Rac1 inhibition or P-Rex1 downregulation increases the …
An Evolutionarily Conserved Rit Gtpase-P38 Mapk Signaling Pathway Mediates Oxidative Stress Resistance, Weikang Cai, Jennifer L. Rudolph, Susan M. W. Harrison, Ling Jin, Aubrey L. Frantz, Douglas A. Harrison, Douglas A. Andres
An Evolutionarily Conserved Rit Gtpase-P38 Mapk Signaling Pathway Mediates Oxidative Stress Resistance, Weikang Cai, Jennifer L. Rudolph, Susan M. W. Harrison, Ling Jin, Aubrey L. Frantz, Douglas A. Harrison, Douglas A. Andres
Molecular and Cellular Biochemistry Faculty Publications
Ras-related small GTP-binding proteins control a wide range of cellular processes by regulating a variety of effector pathways, including prominent roles in the control of mitogen-activated protein kinase (MAPK) cascades. Although the regulatory role(s) for many Ras family GTPases are well established, the physiological function for the Rit/Rin subfamily has been lacking. Here, using both knockout mice and Drosophila models, we demonstrate an evolutionarily conserved role for Rit subfamily GTPases (mammalian Rit and Rin, and the Drosophila RIC homologue) in governing survival in response to oxidative stress. Primary embryonic fibroblasts derived from Rit knockout mice display increased apoptosis and selective …