PRESS-NEWS.org - Press Release Distribution
PRESS RELEASES DISTRIBUTION

No 'brakes' -- Study finds mechanism for increased activity of oncogene in certain cancers

2014-01-07
(Press-News.org) Contact information: Anita Srikameswaran
412-578-9193
University of Pittsburgh Schools of the Health Sciences
No 'brakes' -- Study finds mechanism for increased activity of oncogene in certain cancers PITTSBURGH, Jan. 6, 2014 – The increased activation of a key oncogene in head and neck cancers could be the result of mutation and dysfunction of regulatory proteins that are supposed to keep the gene, which has the potential to cause cancer, in check, according to a new study led by researchers at the University of Pittsburgh School of Medicine. The findings, published in the early online version of the Proceedings of the National Academy of Sciences, suggest a new target for drugs to treat head and neck tumors, as well as other cancers. Many research teams have found activation and increased signaling of a protein known as Signal Transducer and Activator of Transcription 3 (STAT3) in different kinds of cancers, and it is associated with poor prognosis, said senior author Jennifer Grandis, M.D., Distinguished Professor of Otolaryngology, Pitt School of Medicine, and director of the Head and Neck Program at the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC CancerCenter. In adult tissues, STAT3 triggers the production of other proteins that promote the growth and survival of cancer cells. "Until now, the question of why STAT3 could be hyperactivated has gone unanswered," Dr. Grandis said. "Our findings reveal a possible mechanism for this abnormal activity, which could help us develop new cancer drugs." Noting that gene aberrations in STAT3 itself rarely occurred in head and neck cancers, she and her colleagues looked for mutations in other proteins associated with increased activity of STAT3. To be activated, STAT3 must be phosphorylated, meaning a phosphate group is added to it. Many cancer drugs work by inhibiting enzymes called kinases that encourage this process. The team focused instead on the other side of the biochemical seesaw in which enzymes called phosphatases deactivate proteins by removing phosphates. To their surprise, they found head and neck tumors with elevated STAT3 were associated with mutations in the PTPR family of phosphatases. When they reproduced the mutations in computational and lab models, they saw that they led to dysfunction of the enzymes. "Because the phosphatases don't work properly, phosphate groups don't get removed from STAT3 appropriately, and it stays activated," Dr. Grandis explained. "These mutations essentially get rid of the brakes that might otherwise slow or even stop cancer development." It might be possible one day to screen tumors for mutations in the PTPR group and then treat them with drugs that inhibit STAT3's activity, she added. ### Co-investigators include other researchers from the University of Pittsburgh School of Medicine and the University of Pittsburgh Cancer Institute; Central European Institute of Technology at Masaryk University, Czech Republic; University of Texas MD Anderson Cancer Center; Case Western Reserve University; and the Dana-Farber Cancer Institute at Harvard Medical School. The project was funded by National Institutes of Health grants CA097190, CA77308, CA137260, CA127590 and DE024007; the American Cancer Society; the Patricia L. Knebel Fund of the Pittsburgh Foundation; the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine; and the John S. Lazo Cancer Pharmacology Fellowship. About the University of Pittsburgh School of Medicine As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu. http://www.upmc.com/media



ELSE PRESS RELEASES FROM THIS DATE:

'Ardi' skull reveals links to human lineage

2014-01-07
'Ardi' skull reveals links to human lineage The new work expands the catalogue of anatomical similarities linking humans, Australopithecus, and Ardipithecus on the tree of life TEMPE, Ariz.—One of the most hotly debated issues in current human origins research focuses on ...

Suburban sprawl cancels carbon footprint savings of dense urban cores

2014-01-07
Suburban sprawl cancels carbon footprint savings of dense urban cores Interactive maps of US metro areas shows striking differences between cities and suburbs According to a new study by researchers at the University of California, Berkeley, population-dense ...

UW-Madison researchers link protein with breast cancer's spread to the brain

2014-01-07
UW-Madison researchers link protein with breast cancer's spread to the brain MADISON—A cancer-research team at the University of Wisconsin-Madison has identified a protein that may be a major culprit when breast cancer metastasizes to the brain. Brain ...

When danger is in the eye of the beholder

2014-01-07
When danger is in the eye of the beholder UCLA anthropologists study how, why we read into potential peril They went boating alone without life vests and gave no thought to shimmying up very tall coconut trees. And although they were only ...

Novel 'attract-and-kill' approach could help tackle Argentine ants

2014-01-07
Novel 'attract-and-kill' approach could help tackle Argentine ants UC Riverside entomologists devise a technique that involves mixing a synthetic pheromone in insecticide sprays RIVERSIDE, Calif. — After being inadvertently introduced in the United States ...

RAMBO a small but powerful magnet

2014-01-07
RAMBO a small but powerful magnet Rice University system allows high-magnetic-field experiments on a tabletop HOUSTON – (Jan. 6, 2014) – Rice University scientists have pioneered a tabletop magnetic pulse generator that does the work of a room-sized machine – and more. The ...

Discovery spotlights key role of mystery RNA modification in cells

2014-01-07
Discovery spotlights key role of mystery RNA modification in cells Researchers had known for several decades that a certain chemical modification exists on messenger ribonucleic acid (mRNA), which is essential to the flow of genetic information. But only recently ...

Personal health record associated with improved medication adherence

2014-01-07
Personal health record associated with improved medication adherence Patients also saw improved cholesterol levels OAKLAND, Calif. — Patients with diabetes who used an online patient portal to refill medications increased their medication adherence and improved ...

Worker wasps grow visual brains, queens stay in the dark

2014-01-07
Worker wasps grow visual brains, queens stay in the dark Paperwasps in different castes develop different-sized sensory brain structures PHILADELPHIA (Jan. 6, 2014)— A queen in a paperwasp colony largely stays in the dark. The worker wasps, who fly outside to seek food and ...

Babbling babies -- responding to one-on-one 'baby talk' -- master more words

2014-01-07
Babbling babies -- responding to one-on-one 'baby talk' -- master more words AUDIO: A parent demonstrates babytalk ( "parentese ") with child. Click here for ...

LAST 30 PRESS RELEASES:

Thirty-year mystery of dissonance in the “ringing” of black holes explained

Less intensive works best for agricultural soil

Arctic rivers project receives “national champion” designation from frontiers foundation

Computational biology paves the way for new ALS tests

Study offers new hope for babies born with opioid withdrawal syndrome

UT, Volkswagen Group of America celebrate research partnership

New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll

Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes

University of Cincinnati Cancer Center presents research at AACR 2025

Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025

AACR: Researchers share promising results from MD Anderson clinical trials

New research explains why our waistlines expand in middle age

Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker

Chips off the old block

Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia

Cutting the complexity from digital carpentry

Lung immune cell type “quietly” controls inflammation in COVID-19

Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity

State and sociodemographic trends in US cigarette smoking with future projections

Young adults drive historic decline in smoking

NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research

Chimpanzee stem cells offer new insights into early embryonic development

This injected protein-like polymer helps tissues heal after a heart attack

FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology

In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity

Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects

A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions

AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate

Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative

Structure dictates effectiveness, safety in nanomedicine

[Press-News.org] No 'brakes' -- Study finds mechanism for increased activity of oncogene in certain cancers