(Press-News.org) Researchers at University of California, San Diego School of Medicine have discovered a self-regulating loop in the Hippo pathway, a signaling channel garnering increased attention from cancer researchers due to its role in controlling organ size, cell proliferation and cell death.
The finding, published June 26 online in the journal Genes & Development, provides new insights about how the Hippo pathway maintains cellular balance, a subject of growing interest since its malfunction can lead to uncontrolled cell growth and inhibition of cell death - two hallmarks of cancer.
"Since cancer has been associated with overgrowth of cells, dysfunctions in this pathway are being explored in several types of tumors," said Kun-Liang Guan, PhD, professor of pharmacology at UC San Diego School of Medicine and Moores Cancer Center and senior author of the study. Thus far, Guan said the clearest connections have been established in mesothelioma, a type of cancer developed in the protective lining that covers many internal organs of the body, and uveal melanoma, a cancer in the eye - a finding published by Guan's lab in 2014. The Hippo pathway's involvement is also suspected in other cancers.
Guan says the Hippo pathway exists in most body tissues and organs, where it controls the size of organs and tissues by keeping cell growth in check and promoting cell death as needed. For instance, signals transmitted through the Hippo pathway tell the heart to stop growing once it has reached appropriate size. The pathway was first discovered by researchers working in fruit flies in the 1990s. The researchers observed that, when the pathway was removed, the fruit fly grew a large head with skin folds around the neck, reminiscent of a hippopotamus.
While researchers found the pathway interesting from a mechanistic approach, it has only been in recent years that its role and therapeutic potential in cancer began to be explored, said Guan. "A lot of biological pathways have been studied in cancer, but this one is relatively new," he said. "It gained momentum around 2005 when people realized it was also present in the mammalian system. This meant that it's important not only in basic biology, but also in disease pathology."
Guan's lab and others have previously established the key signaling components of the pathway, but its control or braking mechanism - how the pathway shuts off at the proper time - had not been identified until now. "It was already known that YAP and TAZ, two transcription co-activators, work in the Hippo pathway to promote cell growth by inducing certain genes to express," said Guan. In this study, Guan and his team discovered that the two co-activators also have a built-in self-control mechanism that keeps cell growth from getting out of hand. "They have a negative feedback regulation loop that puts the brakes on cell growth."
Specifically, the researchers found that, in addition to promoting genes for cell growth, YAP and TAZ also induce expression of inhibitor genes, such as NF2, that dampen the cell growth signal. "This is important because without this braking mechanism you would get uncontrolled cell growth, which can lead to cancer," Guan said.
The findings, which were made in both cultured cells and mouse tissues, are in keeping with previous studies showing that knocking out the NF2 gene in mice produces uncontrolled cell growth. "Several biotech and pharmaceutical companies are looking at targeting the Hippo pathway for cancer therapy," he said.
Guan said their finding provides "a better picture of how these pathways keep balance, which is important to avoid unchecked signaling that could lead to disease."
INFORMATION:
Co-authors include Toshiro Moroishi, Hyun Woo Park, Zhipeng Meng, Steven W. Plouffe, Koji Taniguchi, and Michael Karin, UCSD; Baodong Qin, UCSD and Second Military Medical University, Shanghai, China; Qian Chen and Duojia Pan, Johns Hopkins University; and Fa-Xing Yu, Fudan University, Shanghai, China.
The research was funded, in part, by grants from the National Institutes of Health (grants EY022611 and CA132809), Japan Society for the Promotion of Science, Yasuda Medical Foundation, and a UC San Diego Cellular and Molecular Pharmacology training grant.
Nashville, Tenn., June 26, 2015--Daily bathing of pediatric patients with disposable cloths containing 2 percent chlorhexidine gluconate (CHG) reduced central line-associated bloodstream infections (CLABSIs) by 59 percent and saved approximately $300,000 in one hospital over a six-month period, according to a new study.
The study, to be presented on Saturday, June 27, at the 42nd Annual Conference of the Association for Professionals in Infection Control and Epidemiology (APIC), examined the impact of implementing a daily CHG bathing protocol for all pediatric patients ...
New research reveals that it only takes two weeks of not using their legs for young people to lose a third of their muscular strength, leaving them on par with a person who is 40-50 years their senior. The Center for Healthy Aging and the Department of Biomedical Sciences at the University of Copenhagen conducted the research.
Time and again, we are told that we need to stay physically active and exercise daily. But how quickly do we actually lose our muscular strength and muscle mass if we go from being averagely active to being highly inactive? For example when we are ...
Scientists at Newcastle University have documented for the first time the DNA damage which can occur to skin across the full range of ultraviolet radiation from the sun providing an invaluable tool for sun-protection and the manufacturers of sunscreen.
Testing on human skin cell lines, this study published today in The Society for Investigative Dermatology, documents the action spectrum of ultraviolet damage in cells derived from both the upper layer (dermis) and lower layer (epidermis) of the skin.
This will allow manufacturers of sunscreen to develop and test products ...
A watershed is a basic unit of the land-surface system and also is a system that exchanges material, energy, and information with the external world while remaining relatively closed within a clear boundary, thereby making it the best unit for theory study and practical applications. Watershed science is an Earth system science practiced on a watershed scale and it has developed rapidly over the previous two decades. The goal of watershed science is to understand and predict the behavior of complex watershed systems and support the sustainable development of watersheds. ...
Food allergies now impacting children of all races and incomes
Hispanic children have highest rise in emergency visits for food allergies
Peanut and tree nuts followed by milk reactions were the most frequent cause of visits
CHICAGO --- Emergency room visits and hospitalizations of children with severe, potentially life-threatening food allergy reactions increased nearly 30 percent in Illinois over five years, reports a Northwestern Medicine study.
Hispanic children, who previously had the lowest reported cases of food allergies, had the biggest increase of emergency ...
A simple new computerised game could help people control their snacking impulses and lose weight. Psychologists at the University of Exeter and Cardiff University have today published a study that shows that participants lost an average of 0.7kg and consumed around 220 fewer calories a day whilst undergoing the week of training.
With 64% of adults in the UK overweight or obese, the research opens up exciting possibilities that 'brain training' techniques specifically targeting problematic behaviours - such as overeating and drinking alcohol - might help people to take ...
A federal preschool program did more than improve educational opportunities for poor children in Mississippi during the 1960s. The program also gave a political and economic boost to the state's civil rights activists, according to a Penn State historian.
A key provision of the federal Economic Opportunity Act of 1964, which paved the way for several federal anti-poverty programs, was aimed at empowering the poor and sidestepping black disenfranchisement in the south, according to Crystal Sanders, an assistant professor of history and African American studies. Sanders ...
A new test can accurately diagnose Ebola virus disease within minutes, providing clinicians with crucial information for treating patients and containing outbreaks.
Researchers from Harvard Medical School, Partners In Health and Boston Children's Hospital have shown that a new commercially developed rapid diagnostic test performed at bedside was as sensitive as the conventional laboratory-based method used for clinical testing during the recent outbreak in Sierra Leone. The results are published in The Lancet.
While the West African Ebola epidemic has slowed since its ...
The class of antidepressants known as SSRIs (selective serotonin reuptake inhibitors), taken to curb menopausal symptoms, may boost bone fracture risk, suggests research published online in the journal Injury Prevention.
The heightened risk seems to last for several years, the findings show, prompting the researchers to suggest that shorter treatment length may be preferable. Further studies are warranted to see if the same association is found at lower doses of these drugs, they say.
SSRIs have become the third most frequently prescribed class of drug in the US, and ...
Recent changes to regulations on the transport of pets across Europe may have increased the threat of introducing rabies from rescue dogs into countries considered free of the disease, suggests research published in Veterinary Record.
In 2012 the European Union (EU) changed its requirements for the non-commercial movement of cats, dogs, and ferrets across the borders of EU and European Economic Area countries.
Up to that point, countries free of rabies virus - the UK, Ireland, Malta, Sweden and Norway - had required an additional blood test to be carried out a month ...
