Virtual Seminar: Src Inhibitory Peptides Based on Connexin43 as a Promising Therapy Against Glioblastoma
Arantxa Tabernero, Ph.D.
Professor of Biochemistry and Molecular Biology
Institute of Neuroscience Castilla y León
University of Salamanca
Virtual Pioneers in Biomedical Research Seminar: Src Inhibitory Peptides Based on Connexin43 as a Promising Therapy Against Glioblastoma
About this Seminar
Glioblastomas are the most frequent primary brain tumors and remain among the most incurable cancers. Connexin43 (Cx43), the main constituent of gap junctions, has been traditionally considered a tumor suppressor protein in glioblastoma; however, Cx43 can also play pro-tumorigenic roles, suggesting that very specific tools should be used to mimic specifically the antitumor effects of Cx43. The C-terminal domain of Cx43 interacts with a plethora of molecules and acts as an intracellular signaling hub. This is the case for the proto-oncoprotein c-Src, which is recruited by Cx43 together with its inhibitors CSK and PTEN. This interaction causes the inhibition of c-Src and its downstream oncogenic pathways. Based on this inhibitory mechanism, Dr. Tabernero and her lab designed a cell-penetrating peptide, TAT-Cx43266-283, that recapitulates the inhibition of c-Src by Cx43. Malignant gliomas have high oncogenic c-Src activity; moreover, cancer stem cells, including glioblastoma stem cells (GSCs), rely on the activity of this oncoprotein for metabolic reprogramming, survival, stemness, and invasion. Importantly, TAT-Cx43266-283 inhibits c-Src activity and consequently exerts potent antitumor effects specifically in glioblastoma cells without affecting healthy brain cells, such as neurons and astrocytes. Interestingly, Tabernero's studies suggest that the mechanism of the antitumor action of TAT-Cx43266-283 involves inhibition of the oncogenic activity of c-Src and not blockade of endogenous Cx43 function. Indeed, the level of Cx43 protein expression is very low and the activity of c-Src is high in TAT-Cx43266-283-targeted cells, such as GSCs, while no effect of TAT-Cx43266-283 on cell viability is found in cells with high expression of Cx43 protein and low activity of c-Src, such as astrocytes. In brief, Tabernero found that TAT-Cx43266-283 reduces migration, invasion, metabolic plasticity and survival in mice and human GSCs, including freshly removed surgical specimens studied as undissociated glioblastoma blocks. Moreover, TAT-Cx43266-283 inhibits c-Src, impairs malignant growth, and enhances survival in mouse models in vivo, without exerting toxicity in endogenous brain cells, supporting the translational potential of this peptide for the treatment of glioblastoma.
This is a free event hosted by the Fralin Biomedical Research Institute and co-sponsored by the institute's Cancer Research Group. The Pioneers in Biomedical Research Seminar Series, which runs annually from September to May, has featured leading biomedical researchers from throughout the country since the program began in 2012. The lectures are also open to all members of the Virginia Tech community including graduate students, undergraduates, faculty, and staff, as well as the public.
You May Also Be Interested In...
Home ItemIn Person Seminar: Quantifying Diverse Research Representation , home
March 31, 2023, 11:00 a.m. | Jonathan Jackson, Ph.D., Executive Director, Community Access, Recruitment, and Engagement (CARE) Research Center, Harvard University and Massachusetts General Hospital | Pioneers in Biomedical Research Seminar Series | Co-Sponsored by the Fralin Biomedical Research Institute Center for Human Neuroscience Research
Home ItemIn Person Lecture: Synaptic Injury: A Link to the Past , home
March 31, 2023, 1 p.m. | Terrance Kummer, M.D., Ph.D., Associate Professor of Neurology, Washington University School of Medicine in St. Louis | Timothy A. Johnson Medical Scholar Lecture Series
Home ItemSeminar: Understanding Cancer: From Development to Therapy , home
April 5, 2023, 11 a.m. | Biplab Dasgupta, M.S., Ph.D., MBA, Professor of Pediatrics, Division of Oncology, Cincinnati Children's Hospital | Seminar
Home ItemIn Person Seminar: Brain Dynamics and Flexible Behaviors , home
April 14, 2023, 11:00 am. | Lucina Q. Uddin, Ph.D., Professor in Residence, Department of Psychiatry and Biobehavioral Science, University of California, Los Angeles | Pioneers in Biomedical Research Seminar Series | Co-Sponsored by the Fralin Biomedical Research Institute Addiction Recovery Research Center and Center for Health Behaviors Research
Home ItemIn Person Lecture: Pathways to Psychosis: Integrating Rare and Common Variants Approaches , home
April 14, 2023, 1 p.m. | Raquel Gur, M.D., Ph.D., Karl and Linda Rickels Professor of Psychiatry, Perelman School of Medicine, University of Pennsylvania | Timothy A. Johnson Medical Scholar Lecture Series
Home ItemIn Person Seminar: Engineering Post-translational Regulation of Ion Channels , home
April 21, 11 a.m. | Henry M. Colecraft, Ph.D., John C. Dalton Professor, Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center | Pioneers in Biomedical Research Seminar Series | Co-Sponsored by the Fralin Biomedical Research Institute Center for Vascular and Heart Research