Breaking News
July 21, 2018 - Digital media use raising risk of ADHD symptoms among the young
July 21, 2018 - Phase 3 study of tanezumab in patients with osteoarthritis pain meets all three co-primary endpoints
July 21, 2018 - Restoring mitochondrial function to reverse aging-related skin wrinkles, hair loss in mice
July 21, 2018 - SP PennTech introduces RW-500 rotary vial washer for biotech, pharmaceutical applications
July 21, 2018 - Researchers to study molecular mechanisms behind susceptibility of males to autism
July 21, 2018 - Fourth Published Clinical Trial Confirms Long-Term Safety of Niagen Supplementation at High Doses and Shows Potential for Improvement in Liver Health
July 21, 2018 - Parents say intense gun violence in PG-13 movies appropriate for teens 15 and older
July 21, 2018 - FAU researchers find possible cause of Parkinson’s disease in the patients’ immune system
July 21, 2018 - Protective qualities of ‘good cholesterol’ reduce after menopause
July 21, 2018 - Researchers develop new way to uncover hidden breast cancer tumors
July 21, 2018 - FDA approves first drug for treatment of adult AML patients with specific genetic mutation
July 21, 2018 - Top AI companies join hands to discover novel drugs for DMD
July 21, 2018 - Ferring announces FDA approval of ZOMACTON for injection in four new pediatric indications
July 20, 2018 - Researchers design proteins that can self-assemble into complex structures
July 20, 2018 - AVITA Medical expands management team to support launch of RECELL device to treat burns
July 20, 2018 - FDA Approves Tibsovo (ivosidenib) for Relapsed or Refractory Acute Myeloid Leukemia with an IDH1 Mutation
July 20, 2018 - Developmental screening and surveillance rates remain low, new study suggests
July 20, 2018 - TGen opens tissue donation portal to advance DIPG research
July 20, 2018 - Health impact of highly processed summertime staples
July 20, 2018 - Exergaming can improve health in overweight and obese children, study shows
July 20, 2018 - Postmenopausal factors may impact heart-protective qualities of ‘good cholesterol’
July 20, 2018 - MRI and blood test combination results in improved prostate cancer diagnosis
July 20, 2018 - Update Health Professional and Consumer on Recent Recalled Products
July 20, 2018 - Researchers trace Parkinson’s damage in the heart
July 20, 2018 - Wearable device designed to measure cortisol in sweat
July 20, 2018 - Scientists demonstrate a new regulation mechanism for skeletal muscles
July 20, 2018 - Exposure to mobile phone radiation may negatively impact memory performance in adolescents
July 20, 2018 - SUSU scientists find alternative method to treat post-traumatic stress disorder syndrome
July 20, 2018 - Gestational diabetes may increase offspring’s heart disease risk
July 20, 2018 - New vaccine could protect unborn babies from Zika virus
July 20, 2018 - Researchers find high mercury and methylmercury concentrations in traditional Tibetan medicine
July 20, 2018 - Brief Safety Plan Intervention in ER Can Cut Suicidal Behavior
July 20, 2018 - Toward a better understanding of Parkinson’s disease
July 20, 2018 - Med school communications office wins four national awards | News Center
July 20, 2018 - Professional baseball players with faster hand-eye coordination may have better batting performance
July 20, 2018 - Study looks into mechanisms that control sleep and wakefulness
July 20, 2018 - Scientists identify melanoma biomarkers that could help tailor immunotherapy treatments
July 20, 2018 - Research reveals long-term efficacy of drug used to treat common cause of kidney failure
July 20, 2018 - Timing of dinner associated with breast and prostate cancer risks
July 20, 2018 - Health Tip: Performing the Heimlich Maneuver
July 20, 2018 - Nearly all adolescents have eating, activity or weight-related issues
July 20, 2018 - Sage launches new web-based tool that helps explore curated genomic analyses of Alzheimer’s
July 20, 2018 - High-performance porous polymeric material for chromatography applications
July 20, 2018 - New molecule shows great promise for future treatment of many cancers
July 20, 2018 - New research project investigates alternative treatments for eye infections
July 20, 2018 - Immune T cells are built to react as fast as possible, shows study
July 20, 2018 - ZHX2 protein could offer a new treatment strategy for kidney cancer
July 20, 2018 - EKF’s Quo-Lab POC HbA1c analyzer meets international quality targets for diabetes testing
July 20, 2018 - Health burdens of very high risk drinking are potentially large, study reveals
July 20, 2018 - Using miniature drug-filled nanocarriers to target headaches and tumors
July 20, 2018 - Researchers uncover cause for progression of prostate cancer to incurable stage
July 20, 2018 - Studies highlight issues regarding black lung, opioid overdose, police violence and more
July 20, 2018 - AbbVie submits supplemental NDA to FDA for venetoclax to treat acute myeloid leukemia
July 20, 2018 - Researchers are one step closer to developing eye drops to treat age-related macular degeneration (AMD)
July 20, 2018 - Patients maintain muscle mass five years after surgically induced weight loss
July 20, 2018 - AMSBIO introduces new, powerful CRISPR/Cas9 gene editing kits
July 20, 2018 - PureTech Health collaborates with Roche to advance oral administration of antisense oligonucleotides
July 20, 2018 - Analysis reveals disparities in cancer death rates among minority groups
July 20, 2018 - Dr Maddy Parsons receives Royal Microscopical Society Life Science Medal
July 20, 2018 - Study finds link between DNA methylation and non-alcoholic fatty liver disease
July 20, 2018 - Military personnel with head trauma and football players with suspected CTE show similar brain changes
July 20, 2018 - Vidac Pharma Announces Initiation of Phase 2b Clinical Trial of VDA-1102 Ointment in Patients with Actinic Keratosis
July 20, 2018 - KKR is buying Envision Healthcare in a nearly $10B deal
July 20, 2018 - Older people with broken bones face higher risk of death for up to 10 years
July 20, 2018 - A simple pill for meth addicts on the cards
July 20, 2018 - UA researchers to repurpose ketamine to reduce side effects in Parkinson’s patients
July 20, 2018 - Child psychiatrist available on call to help assess separated immigrant children
July 20, 2018 - High bitter-taste sensitivity linked to increased risk of cancer
July 20, 2018 - Falling temperatures may lead to rise in numbers of deaths from stroke
July 20, 2018 - Supplemental oxygen prevents rise in morning blood pressure in OSA patients
July 20, 2018 - High fruit and vegetable intake linked to reduced risk of breast cancer
July 20, 2018 - Careful patient selection may help achieve good outcomes for vaginal mesh surgery
July 20, 2018 - Researchers raise viability of cloned mice using somatic cell nuclear transfer method
July 20, 2018 - 3HP for Latent TB Infection Treatment | 2018 | Newsroom | NCHHSTP
July 20, 2018 - An orange a day keeps macular degeneration away: 15-year study
July 20, 2018 - Researchers elucidate how the brain drives trial-by-trial adaptation to compensate for errors
July 20, 2018 - Understanding triple-negative breast cancer to develop better treatments
July 20, 2018 - Study compares outpatient antibiotic prescribing with traditional medical, retail clinic settings
July 20, 2018 - Immediate Monitoring With ECG Patch Ups A-Fib Diagnosis Rate
July 20, 2018 - KHN’s ‘What the Health?’ Drug prices and unicorns
Salk scientists discover protein that ‘turns off’ uncontrolled liver cancer growth

Salk scientists discover protein that ‘turns off’ uncontrolled liver cancer growth

image_pdfDownload PDFimage_print

Salk Institute scientists, together with researchers from Switzerland’s University of Basel and University Hospital Basel, discovered a protein called LHPP that acts as a molecular switch to turn off the uncontrolled growth of cells in liver cancer. The tumor suppressor, which could be useful as a biomarker to help diagnose and monitor treatment for liver cancer, could also be relevant for other cancer types. The work appeared in print in the journal Nature on March 29, 2018, and adds to the growing body of knowledge about cellular processes that either promote or prevent cancer.

“I think we’ve discovered a new control mechanism for cell proteins that, when disrupted, could be a driver for cancer,” says Tony Hunter, Salk’s American Cancer Society Professor and an author on the new paper. “It’s exciting because it offers the possibility of new therapeutics or new diagnostics for a cancer that’s basically untreatable–liver cancer–and potentially others, as well.”

Hunter is known for his 1979 discovery of a molecular signaling process called tyrosine phosphorylation. In this process, proteins called kinases attach the chemical phosphate–like a sticky note–to the amino acid tyrosine in target proteins. But, when dysfunctional, tyrosine phosphorylation can also turn on the uncontrolled cell growth that leads to cancer. Hunter’s breakthrough opened the door to the development of a new class of anti-cancer pharmaceuticals called tyrosine kinase inhibitors, including the life-saving leukemia drug Gleevec.

Since then, Hunter’s lab has continued to study the process of phosphorylation, not only in terms of adding phosphates (via kinases or “on switches”) but also removing them (via proteins called phosphatases or “off switches”). In 2015, his team developed an antibody to identify and study phosphates bonded to another amino acid called histidine.

In the new work, the international team, led by Professor Michael Hall of the Biozentrum, University of Basel, examined these switches in a mouse model of the most common form of primary liver cancer–hepatocellular carcinoma. To compare tumor cells with normal cells, the team analyzed more than 4,000 proteins in healthy and diseased liver tissue. By the end, three proteins stood out: the histidine kinases NME1 and NME2 were elevated in tumor cells, and the suspected histidine phosphatase LHPP was deficient.

“It is striking that LHPP is present in healthy tissue and completely absent in tumor tissue,” says Sravanth Hindupur, a postdoctoral researcher at the University of Basel and the paper’s first author. That gave the researchers a clue to explore histidine phosphorylation as a potential cancer target. Indeed, they found that the levels of protein phosphorylated in histidine were significantly higher in the tumor tissue than in normal liver tissue.

NME1 and NME2 are known histidine kinases and LHPP had been suspected to be a histidine phosphatase. With further experiments, the team verified that not only is LHPP a histidine phosphatase, but it is also a tumor suppressor–essentially an “off” switch for cancer. Reintroducing LHPP into the liver of the model mice destined to develop tumors prevented the formation of tumors.

When the researchers next examined samples from human liver tumors, they found a similar pattern: NME1 and 2 levels were high and LHPP was low compared to healthy liver tissue. Furthermore, the Cancer Genome Atlas database, a collection of RNA sequences obtained from different human cancers, showed that a significant fraction of human liver cancers have low levels of LHPP, and that both disease severity and life expectancy are correlated with LHPP levels.

“The parallels between tyrosine phosphorylation and histidine phosphorylation are what really got me interested in the project,” adds Hunter. “Whether this can be used as a therapeutic avenue, I don’t know. But the fact that it could be so disease-relevant motivates me.”

Source:

Tumor suppressor protein targets liver cancer

Tagged with:

About author

Related Articles