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Full-Text Articles in Medicine and Health Sciences
Metabolic Pathways And Targets In Chondrosarcoma, Ida Micaily, Megan E Roche, Mohammad Y Ibrahim, Ubaldo E. Martinez-Outshoorn, Atrayee Basu Mallick
Metabolic Pathways And Targets In Chondrosarcoma, Ida Micaily, Megan E Roche, Mohammad Y Ibrahim, Ubaldo E. Martinez-Outshoorn, Atrayee Basu Mallick
Department of Medical Oncology Faculty Papers
Chondrosarcomas are the second most common primary bone malignancy. Chondrosarcomas are characterized by the production of cartilaginous matrix and are generally resistant to radiation and chemotherapy and the outcomes are overall poor. Hence, there is strong interest in determining mechanisms of cancer aggressiveness and therapeutic resistance in chondrosarcomas. There are metabolic alterations in chondrosarcoma that are linked to the epigenetic state and tumor microenvironment that drive treatment resistance. This review focuses on metabolic changes in chondrosarcoma, and the relationship between signaling via isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2), hedgehog, PI3K-mTOR-AKT, and SRC, as well as histone acetylation and …
Myc-Mediated Transcriptional Regulation Of The Mitochondrial Chaperone Trap1 Controls Primary And Metastatic Tumor Growth., Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Jagadish C. Ghosh, Andrew V Kossenkov, Hsin-Yao Tang, Shiv Ram Krishn, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri
Myc-Mediated Transcriptional Regulation Of The Mitochondrial Chaperone Trap1 Controls Primary And Metastatic Tumor Growth., Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Jagadish C. Ghosh, Andrew V Kossenkov, Hsin-Yao Tang, Shiv Ram Krishn, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri
Department of Cancer Biology Faculty Papers
The role of mitochondria in cancer continues to be debated, and whether exploitation of mitochondrial functions is a general hallmark of malignancy or a tumor- or context-specific response is still unknown. Using a variety of cancer cell lines and several technical approaches, including siRNA-mediated gene silencing, ChIP assays, global metabolomics and focused metabolite analyses, bioenergetics, and cell viability assays, we show that two oncogenic Myc proteins, c-Myc and N-Myc, transcriptionally control the expression of the mitochondrial chaperone TNFR-associated protein- 1 (TRAP1) in cancer. In turn, this Myc-mediated regulation preserved the folding and function of mitochondrial oxidative phosphorylation (OXPHOS) complex II …
Metformin As A Therapeutic Target In Endometrial Cancers., Teresa Lee, Ubaldo E. Martinez-Outshoorn, Russell J. Schilder, Christine H. Kim, Scott D. Richard, Norman G. Rosenblum, Jennifer Johnson
Metformin As A Therapeutic Target In Endometrial Cancers., Teresa Lee, Ubaldo E. Martinez-Outshoorn, Russell J. Schilder, Christine H. Kim, Scott D. Richard, Norman G. Rosenblum, Jennifer Johnson
Department of Medical Oncology Faculty Papers
Endometrial cancer is the most common gynecologic malignancy in developed countries. Its increasing incidence is thought to be related in part to the rise of metabolic syndrome, which has been shown to be a risk factor for the development of hyperestrogenic and hyperinsulinemic states. This has consequently lead to an increase in other hormone-responsive cancers as well e.g., breast and ovarian cancer. The correlation between obesity, hyperglycemia, and endometrial cancer has highlighted the important role of metabolism in cancer establishment and persistence. Tumor-mediated reprogramming of the microenvironment and macroenvironment can range from induction of cytokines and growth factors to stimulation …
Monocarboxylate Transporter 4 (Mct4) Knockout Mice Have Attenuated 4nqo Induced Carcinogenesis; A Role For Mct4 In Driving Oral Squamous Cell Cancer., Sara Bisetto, Diana Whitaker Menezes, Nicole A. Wilski, Madalina Tuluc, Joseph Curry, Tingting Zhan, Christopher M. Snyder, Ubaldo E. Martinez-Outshoorn, Nancy J. Philp
Monocarboxylate Transporter 4 (Mct4) Knockout Mice Have Attenuated 4nqo Induced Carcinogenesis; A Role For Mct4 In Driving Oral Squamous Cell Cancer., Sara Bisetto, Diana Whitaker Menezes, Nicole A. Wilski, Madalina Tuluc, Joseph Curry, Tingting Zhan, Christopher M. Snyder, Ubaldo E. Martinez-Outshoorn, Nancy J. Philp
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Head and neck squamous cell carcinoma (HNSCC) is the 6th most common human cancer and affects approximately 50,000 new patients every year in the US. The major risk factors for HNSCC are tobacco and alcohol consumption as well as oncogenic HPV infections. Despite advances in therapy, the overall survival rate for all-comers is only 50%. Understanding the biology of HNSCC is crucial to identifying new biomarkers, implementing early diagnostic approaches and developing novel therapies. As in several other cancers, HNSCC expresses elevated levels of MCT4, a member of the SLC16 family of monocarboxylate transporters. MCT4 is a H+-linked …
Celecoxib Concentration Predicts Decrease In Prostaglandin E2 Concentrations In Nipple Aspirate Fluid From High Risk Women, Edward R. Sauter, Wenyi Qin, John E. Hewett, Rachel L. Ruhlen, John T. Flynn, George Rottinghaus, Yin-Chieh Chen
Celecoxib Concentration Predicts Decrease In Prostaglandin E2 Concentrations In Nipple Aspirate Fluid From High Risk Women, Edward R. Sauter, Wenyi Qin, John E. Hewett, Rachel L. Ruhlen, John T. Flynn, George Rottinghaus, Yin-Chieh Chen
Department of Molecular Physiology and Biophysics Faculty Papers
BACKGROUND: Epidemiologic studies suggest that long term low dose celecoxib use significantly lowers breast cancer risk. We previously demonstrated that 400 mg celecoxib taken twice daily for 2 weeks lowered circulating plasma and breast nipple aspirate fluid (NAF) prostaglandin (PG)E2 concentrations in post- but not premenopausal high risk women. We hypothesized that circulating concentrations of celecoxib influenced PGE2 response, and that plasma levels of the drug are influenced by menopausal status. To address these hypotheses, the aims of the study were to determine: 1) if circulating plasma concentrations of celecoxib correlated with the change in plasma or NAF PGE2 concentrations …
Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki
Phosphorylation-Induced Conformational Switching Of Cpi-17 Produces A Potent Myosin Phosphatase Inhibitor, Masumi Eto, Toshio Kitazawa, Fumiko Matsuzawa, Sei-Ichi Aikawa, Jason A. Kirkbride, Noriyoshi Isozumi, Yumi Nishimura, David L. Brautigan, Shin-Ya Ohki
Department of Molecular Physiology and Biophysics Faculty Papers
Phosphorylation of endogenous inhibitor proteins specific for type-1 Ser/Thr phosphatase (PP1) provides a mechanism for reciprocal coordination of kinase and phosphatase activities. Phosphorylation of Thr38 in the inhibitor protein CPI-17 transduces G-protein-mediated signaling into a > 1000-fold increase of inhibitory potency toward myosin phosphatase. We show here the solution NMR structure of phospho-T38-CPI-17 with r. m. s. d. of 0.36 ± 0.06 Å for the backbone secondary structure, which reveals how phosphorylation triggers a conformational change and exposes the PP1 inhibitory surface. This active conformation is stabilized by the formation of a hydrophobic core of intercalated side-chains, which is not formed …
Association Of The Tensin N-Terminal Protein-Tyrosine Phosphatase Domain With The Alpha Isoform Of Protein Phosphatase-1 In Focal Adhesions, Masumi Eto, Jason Kirkbride, Elizabeth Elliott, Su Hao Lo, David L. Brautigan
Association Of The Tensin N-Terminal Protein-Tyrosine Phosphatase Domain With The Alpha Isoform Of Protein Phosphatase-1 In Focal Adhesions, Masumi Eto, Jason Kirkbride, Elizabeth Elliott, Su Hao Lo, David L. Brautigan
Department of Molecular Physiology and Biophysics Faculty Papers
Focal adhesions attach cultured cells to the extracellular matrix, and we found endogenous protein phosphatase-1alpha isoform (PP1alpha) localized in adhesions across the entire area of adherent fibroblasts. However, in fibroblasts migrating into a scrape wound or spreading after replating PP1alpha did not appear in adhesions near the leading edge but was recruited into other adhesions coincident in time and space with incorporation of tensin. Endogenous tensin and PP1alpha co-precipitated from cell lysates with isoform-specific PP1 antibodies. Chemical cross-linking of focal adhesion preparations with Lomant's reagent demonstrated molecular proximity of endogenous PP1alpha and tensin, whereas neither focal adhesion kinase nor vinculin …