Breaking News
May 3, 2019 - Vaping and Smoking May Signal Greater Motivation to Quit
May 3, 2019 - Dementia looks different in brains of Hispanics
May 3, 2019 - Short-Staffed Nursing Homes See Drop In Medicare Ratings
May 3, 2019 - Study of teens with eating disorders explores how substance users differ from non-substance users
May 3, 2019 - Scientists develop new video game that may help in the study of Alzheimer’s
May 3, 2019 - Arc Bio introduces Galileo Pathogen Solution product line at ASM Clinical Virology Symposium
May 3, 2019 - Cornell University study uncovers relationship between starch digestion gene and gut bacteria
May 3, 2019 - How to Safely Use Glucose Meters and Test Strips for Diabetes
May 3, 2019 - Anti-inflammatory drugs ineffective for prevention of Alzheimer’s disease
May 3, 2019 - Study tracks Pennsylvania’s oil and gas waste-disposal practices
May 3, 2019 - Creating a better radiation diagnostic test for astronauts
May 3, 2019 - Vegans are often deficient in these four nutrients
May 3, 2019 - PPDC announces seed grants to develop medical devices for children
May 3, 2019 - Study maps out the frequency and impact of water polo head injuries
May 3, 2019 - Research on Reddit identifies risks associated with unproven treatments for opioid addiction
May 3, 2019 - Good smells may help ease tobacco cravings
May 3, 2019 - Medical financial hardship found to be very common among people in the United States
May 3, 2019 - Researchers develop multimodal system for personalized post-stroke rehabilitation
May 3, 2019 - Study shows significant mortality benefit with CABG over percutaneous coronary intervention
May 3, 2019 - Will gene-editing of human embryos ever be justifiable?
May 3, 2019 - FDA Approves Dengvaxia (dengue vaccine) for the Prevention of Dengue Disease in Endemic Regions
May 3, 2019 - Why Tonsillitis Keeps Coming Back
May 3, 2019 - Fighting the opioid epidemic with data
May 3, 2019 - Maggot sausages may soon be a reality
May 3, 2019 - Deletion of ATDC gene prevents development of pancreatic cancer in mice
May 2, 2019 - Targeted Therapy Promising for Rare Hematologic Cancer
May 2, 2019 - Alzheimer’s disease is a ‘double-prion disorder,’ study shows
May 2, 2019 - Reservoir bugs: How one bacterial menace makes its home in the human stomach
May 2, 2019 - Clinical, Admin Staff From Cardiology Get Sneak Peek at Epic
May 2, 2019 - Depression increases hospital use and mortality in children
May 2, 2019 - Vicon and NOC support CURE International to create first gait lab in Ethiopia
May 2, 2019 - Researchers use 3D printer to make paper organs
May 2, 2019 - Viral infection in utero associated with behavioral abnormalities in offspring
May 2, 2019 - U.S. Teen Opioid Deaths Soaring
May 2, 2019 - Opioid distribution data should be public
May 2, 2019 - In the Spotlight: “I’m learning every single day”
May 2, 2019 - 2019 Schaefer Scholars Announced
May 2, 2019 - Podcast: KHN’s ‘What The Health?’ Bye-Bye, ACA, And Hello ‘Medicare-For-All’?
May 2, 2019 - Study describes new viral molecular evasion mechanism used by cytomegalovirus
May 2, 2019 - SLU study suggests a more equitable way for Medicare reimbursement
May 2, 2019 - Scientists discover first gene involved in lower urinary tract obstruction
May 2, 2019 - Researchers identify 34 genes associated with increased risk of ovarian cancer
May 2, 2019 - Many low-income infants receive formula in the first few days of life, finds study
May 2, 2019 - Global study finds high success rate for hip and knee replacements
May 2, 2019 - Taking depression seriously: What is it?
May 2, 2019 - With Head Injuries Mounting, Will Cities Put Their Feet Down On E-Scooters?
May 2, 2019 - Scientists develop small fluorophores for tracking metabolites in living cells
May 2, 2019 - Study casts new light into how mothers’ and babies’ genes influence birth weight
May 2, 2019 - Researchers uncover new brain mechanisms regulating body weight
May 2, 2019 - Organ-on-chip systems offered to Asia-Pacific regions by Sydney’s AXT
May 2, 2019 - Adoption of new rules drops readmission penalties against safety net hospitals
May 2, 2019 - Kids and teens who consume zero-calorie sweetened beverages do not save calories
May 2, 2019 - Improved procedure for cancer-related erectile dysfunction
May 2, 2019 - Hormone may improve social behavior in autism
May 2, 2019 - Alzheimer’s disease may be caused by infectious proteins called prions
May 2, 2019 - Even Doctors Can’t Navigate Our ‘Broken Health Care System’
May 2, 2019 - Study looks at the impact on criminal persistence of head injuries
May 2, 2019 - Honey ‘as high in sugars as table sugar’
May 2, 2019 - Innovations to U.S. food system could help consumers in choosing healthy foods
May 2, 2019 - FDA Approves Mavyret (glecaprevir and pibrentasvir) as First Treatment for All Genotypes of Hepatitis C in Pediatric Patients
May 2, 2019 - Women underreport prevalence and intensity of their own snoring
May 2, 2019 - Concussion summit focuses on science behind brain injury
May 2, 2019 - Booker’s Argument For Environmental Justice Stays Within The Lines
May 2, 2019 - Cornell research explains increased metastatic cancer risk in diabetics
May 2, 2019 - Mount Sinai study provides fresh insights into cellular pathways that cause cancer
May 2, 2019 - Researchers to study link between prenatal pesticide exposures and childhood ADHD
May 2, 2019 - CoGEN Congress 2019: Speakers’ overviews
May 2, 2019 - A new strategy for managing diabetic macular edema in people with good vision
May 2, 2019 - Sagent Pharmaceuticals Issues Voluntary Nationwide Recall of Ketorolac Tromethamine Injection, USP, 60mg/2mL (30mg per mL) Due to Lack of Sterility Assurance
May 2, 2019 - Screen time associated with behavioral problems in preschoolers
May 2, 2019 - Hormone reduces social impairment in kids with autism | News Center
May 2, 2019 - Researchers synthesize peroxidase-mimicking nanozyme with low cost and superior catalytic activity
May 2, 2019 - Study results of a potential drug to treat Type 2 diabetes in children announced
May 2, 2019 - Multigene test helps doctors to make effective treatment decisions for breast cancer patients
May 2, 2019 - UNC School of Medicine initiative providing unique care to dementia patients
May 2, 2019 - Nestlé Health Science and VHP join forces to launch innovative COPES program for cancer patients
May 2, 2019 - Study examines how our brain generates consciousness and loses it during anesthesia
May 2, 2019 - Transition Support Program May Aid Young Adults With Type 1 Diabetes
May 2, 2019 - Study shows how neutrophils exacerbate atherosclerosis by inducing smooth muscle-cell death
May 2, 2019 - Research reveals complexity of how we make decisions
Researchers discover new promising target point for cancer and diabetes therapies

Researchers discover new promising target point for cancer and diabetes therapies

If certain signaling cascades are misregulated, diseases like cancer, obesity and diabetes may occur. A mechanism recently discovered by scientists at the Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) in Berlin and at the University of Geneva has a crucial influence on such signaling cascades and may be an important key for the future development of therapies against these diseases. The results of the study have just been published in the prestigious scientific journal Molecular Cell.

Cell growth and cell differentiation as well as the release and efficacy of hormones such as insulin depend on the presence of lipids. Lipids are small molecules resembling fat. They are the building blocks of cell membranes, and they also serve as molecular switches in signaling cascades. Such cascades play a crucial role in the control of cell growth and division as well as in differentiation processes such as the formation of new blood vessels referred to as angiogenesis. If signaling cascades are disturbed, diseases such as cancer or metabolic disorders such as obesity and diabetes can occur. The ability to influence the enzymes involved in the biosynthesis of signaling lipids in cells could thus serve as a starting point for the treatment of these diseases.

The team around Professor Dr. Volker Haucke at the FMP pursued this approach: Years of work allowed the team to successfully express and purify the lipid kinase PI3KC2A and to analyze the enzyme in detail. The PI3KC2A kinase enzyme performs crucial functions in receptor uptake, cell division, the release of and signaling by insulin, and in angiogenesis. Together with Dr. Oscar Vadas of the University of Geneva, the FMP Team performed intricate studies on the structural biology and cell biology of the kinase. Their studies revealed an initially inactive, auto-inhibited form of the PI3KC2A kinase in the cytoplasm of cells. External signals can then activate the kinase as it becomes recruited to the cell membrane. Such signaling cascades are initiated by the docking of protein ligands such as insulin or growth factors to receptors in the cell membrane. The ligand-bound receptors become activated and transmit signals into the cell interior. This receptor signaling process is accompanied by the invagination of the cell membrane to eventually form vesicles that deliver the active membrane-bound receptor into the cytoplasm. Lipid kinases such as PI3KC2A participate in the process of vesicle formation and in the signaling cascades inside the cell.

For the first time, the team of scientists was able to observe the transition of PI3KC2A from the inactive into an active form. Dr. Oscar Vadas describes this mechanism: “In its inactive form, the kinase exists rolled up looking as if it had wrapped its ‘arms’ around itself. In order to activate the kinase, two specific components of the cell membrane have to be in the same location at the same time. When this happens, the kinase unfolds its ‘arms’, and each ‘arm’ binds to one of the two components”. The activated kinase within seconds synthesizes many signaling lipid molecules. In turn, these signaling lipids control the uptake of activated signaling receptors into the cell (image) and thereby regulate processes such as cell growth, division and differentiation.

These findings are of great importance for basic research as the Berlin/Geneva team has provided unprecedented molecular insight into the central cellular process of receptor uptake. Moreover, the scientific work presents a major leap toward the pharmacological manipulation of PI3KC2A and related kinases. “For the first time, we have a handle on a mechanism, which may eventually enable us to alter PI3KC2A lipid kinase activity. This may provide a direct target for therapies”, emphasizes Professor Dr. Volker Haucke. For example, small molecules that block PI3KC2A activity could serve as anti-tumor agents given that angiogenesis is important for nutrient supply to tumors. As studies with mice suggest, the pharmacological inhibition of PI3KC2A activity should bring angiogenesis to a stop. The FMP scientists in Berlin are now looking for such agents.

“We have discovered a new promising target and are keen to further explore its therapeutic potential”, promises Professor Dr. Volker Haucke referring to the initiated compound search. While the FMP does not develop drugs itself, the institute aims to provide new leads for future drug development. Professor Haucke is confident: “In this case, we expect to identify candidate molecules that may at some point in the future become clinically useful.”

Source:

http://www.leibniz-fmp.de/press-media/press-releases/press-releases-single-view1/article/a-molecular-switch-may-serve-as-new-target-point-for-cancer-and-diabetes-therapies.html

Tagged with:

About author

Related Articles