Cancer gene plays key role in cystic fibrosis lung infections

December 12, 2017, Columbia University Medical Center

PTEN is best known as a tumor suppressor, a type of protein that protects cells from growing uncontrollably and becoming cancerous. But according to a new study from Columbia University Medical Center (CUMC), PTEN has a second, previously unknown talent: working with another protein, CFTR, it also keeps lung tissue free and clear of potentially dangerous infections.

The findings, published in Immunity, explain why people with cystic are particularly prone to respiratory infections—and suggest a new approach to treatment.

A quarter-century ago, researchers discovered that cystic fibrosis is caused by mutations in the CFTR gene, which makes an eponymous protein that transports chloride ions in and out of the cell. Without ion transport, mucus in the lung becomes thicker and stickier and traps bacteria—especially Pseudomonas—in the lung. The trapped bacteria exacerbate the body's inflammatory response, leading to persistent, debilitating infections.

But newer research suggests CFTR mutations also encourage infections through a completely different manner.

"Recent findings suggested that with CFTR mutations have a weaker response to bacteria, reducing their ability to clear infections and augmenting inflammation," said lead author Sebastián A. Riquelme, PhD, a postdoctoral fellow at CUMC. "This was interesting because it pointed to a parallel deregulated immune mechanism that contributes to airway destruction, beyond CFTR's effect on mucus."

That's where PTEN comes into play. "We had no idea that PTEN was involved in cystic fibrosis," said study leader Alice Prince, MD, professor of pediatrics (in pharmacology). "We were studying mice that lack a form of PTEN and noticed that they had a severe inflammatory response to Pseudomonas and diminished clearance that looked a lot like what we see in patients with cystic fibrosis."

Delving deeper, the CUMC team discovered that when PTEN is located on the surface of lung and immune cells, it helps clear Pseudomonas bacteria and keeps the inflammatory response in check. But PTEN can do this only when it's attached to CFTR.

And in most cases of cystic fibrosis, little CFTR finds it way to the cell surface. As a result, the duo fail to connect, and Pseudomonas run wild.

As it happens, the latest generation of cystic fibrosis drugs push mutated CFTR to the cell surface, with the aim of improving chloride channel function and reducing a buildup of mucus. The new findings suggest that it might be beneficial to coax nonfunctional CFTR to the surface as well, since even abnormal CFTR can work with PTEN to fight infections, according to the researchers.

"Another idea is to find drugs that improve PTEN membrane anti-inflammatory activity directly," said Dr. Riquelme. "There are several PTEN promotors under investigation as cancer treatments that might prove useful in cystic fibrosis."

The study also raises the possibility that PTEN might have something to do with the increased risk of gastrointestinal cancer in . "With better clinical care, these patients are living much longer, and we're seeing a rise in gastrointestinal cancers," said Dr. Prince. "Some studies suggest that CFTR may be a tumor suppressor. Our work offers an alternative hypothesis, where CFTR mutations and lack of its partner, PTEN, might be driving this cancer in patients with ."

The paper is titled, "Cystic fibrosis transmembrane conductance regulator attaches tumor suppressor PTEN to the membrane and promotes anti Pseudomonas aeruginosa immunity."

Explore further: Discovery of a key molecule for improving cystic fibrosis treatments

Related Stories

Discovery of a key molecule for improving cystic fibrosis treatments

December 12, 2017
Researchers at the University of Montreal Hospital Research Centre (CRCHUM) have identified a promising solution to improving treatments offered to patients with cystic fibrosis.

Cystic fibrosis scientists discover abnormal response to lung infections

October 6, 2017
"For a very long time, there has been discussion about whether cystic fibrosis was a bacteria-infection problem, an inflammation problem, or an immune system problem," said Juan Ianowski, the lead author of the paper published ...

Cystic fibrosis study offers new understanding of silent changes in genes

May 17, 2017
Researchers studying the root cause of cystic fibrosis have made a major advance in our understanding of silent gene changes with implications for the complexity of cystic fibrosis. The findings are published today in [16 ...

Benefits of cystic fibrosis drug ivacaftor reported in pre-school children for the first time

January 21, 2016
The oral drug ivacaftor appears to be safe and could be beneficial to young children between the ages of 2 and 5 with a specific type of cystic fibrosis, according to new research published in The Lancet Respiratory Medicine ...

Tezacaftor-ivacaftor, ivacaftor alone effective in CF

November 7, 2017
(HealthDay)—Tezacaftor-ivacaftor or ivacaftor alone is effective for patients with cystic fibrosis who are heterozygous for the Phe508del deletion, and tezacaftor-ivacaftor is effective for patients who are homozygous for ...

New simple test could help cystic fibrosis patients find best treatment

November 21, 2017
Several cutting-edge treatments have become available in recent years to correct the debilitating chronic lung congestion associated with cystic fibrosis. While the new drugs are life-changing for some patients, they do not ...

Recommended for you

Novel genomic tools provide new insight into human immune system

January 19, 2018
When the body is under attack from pathogens, the immune system marshals a diverse collection of immune cells to work together in a tightly orchestrated process and defend the host against the intruders. For many decades, ...

Genomics reveals key macrophages' involvement in systemic sclerosis

January 18, 2018
A new international study has made an important discovery about the key role of macrophages, a type of immune cell, in systemic sclerosis (SSc), a chronic autoimmune disease which currently has no cure.

First vaccine developed against grass pollen allergy

January 18, 2018
Around 400 million people worldwide suffer in some form or other from a grass pollen allergy (rhinitis), with the usual symptoms of runny nose, cough and severe breathing problems. In collaboration with the Viennese firm ...

Researchers discover key driver of atopic dermatitis

January 17, 2018
Severe eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition that is driven by an allergic reaction. In their latest study, researchers at La Jolla Institute reveal an important player that promotes ...

Who might benefit from immunotherapy? New study suggests possible marker

January 16, 2018
While immunotherapy has made a big impact on cancer treatment, the fact remains that only about a quarter of patients respond to these treatments.

Researchers identify new way to unmask melanoma cells to the immune system

January 16, 2018
system, which enables these deadly skin cancers to grow and spread.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.