Nav: Home

Rare driver mutations disrupt NOTCH signaling to promote squamous cell carcinoma

March 12, 2020

Head and neck squamous cell carcinoma (HNSCC) - a group of cancers that affect the the mouth, nose and throat - is a disease driven by mutations in the NOTCH tumor suppressor signaling pathway, according to a new study. It reveals the identity of rare driver mutations in tumor-suppressing genes using a mouse-based in vivo CRISPR screen to evaluate the function of so-called "long tail" mutations. In humans, these mutations are present in 67% of HNSCC patients and converge on NOTCH inactivation, thus promoting tumor development. HNSCC is the 6th most common human cancer and, while curable, has a poor survival rate and claims the lives of roughly 350,000 people worldwide each year. Like other cancers, HNSCC is characterized by a few genes mutated at high frequency in many patients (including the NOTCH tumor suppressor gene), followed by a "long-tail" of hundreds of other individually rare mutations observed in only a few patients. The functional consequences and biological significance of recurrent but rare mutations are generally unknown, but these mutations could potentially shed light on cancer biology and tumor evolution and perhaps lead to novel treatment strategies. Sampath Loganathan and colleagues developed a reverse genetic CRISPR screen that allowed them to identify genes that, upon mutation, predispose mice to developing MNSCC. Through their analysis, Loganathan et al. identified 15 potent tumor suppressor genes that, when mutated, triggered rapid growth of HNSCC in the mice. These genes included ADAM10 and AJUBA, which are also mutated in human HNSCC. The wild type versions of ADAM10 and AJUBA promote NOTCH signaling. These results show that HNSCC-associated mutations converge on inactivation of the NOTCH tumor suppressor signaling pathway.
-end-


American Association for the Advancement of Science

Related Tumor Articles:

How do tumor cells divide in the crowd?
Scientists led by Dr. Elisabeth Fischer-Friedrich, group leader at the Excellence Cluster Physics of Life (PoL) and the Biotechnology Center TU Dresden (BIOTEC) studied how cancer cells are able to divide in a crowded tumor tissue and connected it to the hallmark of cancer progression and metastasis, the epithelial-mesenchymal transition (EMT).
Finding a way to STING tumor growth
The immune protein STING has long been noted for helping protect against viruses and tumors by signaling a well-known immune molecule.
Assembly within the tumor center
Number of macrophages in tumor tissue enables prognosis of lung tumor progression.
Mirror image tumor treatment
Our immune system ought to be able to recognize and kill tumor cells.
Traces of immortality in tumor DNA
To gain an infinite lifespan, cancer cells need to maintain the ends of their chromosomes, known as telomeres.
Peering into the genome of brain tumor
Scientists at Osaka University have created a machine learning method for classifying the mutations of glioma brain tumors based on MR images alone.
Glutamine-blocking drug slows tumor growth and strengthens anti-tumor response
A compound developed by Johns Hopkins researchers that blocks glutamine metabolism can slow tumor growth, alter the tumor microenvironment and promote the production of durable and highly active anti-tumor T cells.
Cancer genes and the tumor milieu
In a recent study published in Cancer Research, researchers demonstrate the role of an oncogene in altering the immediate environment of tumors.
Mechanism of tumor metastasis and tumor-suppressive role of UDP-glucose revealed
Scientists from Dalian Institute of Chemical Physics (DICP) and Shanghai Institute of Biochemistry and Cell Biology (SIBCB) of the Chinese Academy of Sciences revealed that UDP-glucose accelerates SNAI1 mRNA decay and impairs lung cancer metastasis.
The fluid that feeds tumor cells
MIT biologists have found that the nutrient composition of the interstitial fluid that normally surrounds pancreatic tumors is different from that of the culture medium normally used to grow cancer cells.
More Tumor News and Tumor Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Debbie Millman: Designing Our Lives
From prehistoric cave art to today's social media feeds, to design is to be human. This hour, designer Debbie Millman guides us through a world made and remade–and helps us design our own paths.
Now Playing: Science for the People

#574 State of the Heart
This week we focus on heart disease, heart failure, what blood pressure is and why it's bad when it's high. Host Rachelle Saunders talks with physician, clinical researcher, and writer Haider Warraich about his book "State of the Heart: Exploring the History, Science, and Future of Cardiac Disease" and the ails of our hearts.
Now Playing: Radiolab

Insomnia Line
Coronasomnia is a not-so-surprising side-effect of the global pandemic. More and more of us are having trouble falling asleep. We wanted to find a way to get inside that nighttime world, to see why people are awake and what they are thinking about. So what'd Radiolab decide to do?  Open up the phone lines and talk to you. We created an insomnia hotline and on this week's experimental episode, we stayed up all night, taking hundreds of calls, spilling secrets, and at long last, watching the sunrise peek through.   This episode was produced by Lulu Miller with Rachael Cusick, Tracie Hunte, Tobin Low, Sarah Qari, Molly Webster, Pat Walters, Shima Oliaee, and Jonny Moens. Want more Radiolab in your life? Sign up for our newsletter! We share our latest favorites: articles, tv shows, funny Youtube videos, chocolate chip cookie recipes, and more. Support Radiolab by becoming a member today at Radiolab.org/donate.