LIFR protein suppresses breast cancer metastasis

September 25, 2012

A receptor protein suppresses local invasion and metastasis of breast cancer cells, the most lethal aspect of the disease, according to a research team headed by scientists from The University of Texas MD Anderson Cancer Center.

Reporting in Nature Medicine, the team described using high-throughput RNA sequencing to identify the leukemia inhibitory factor receptor (LIFR) as a novel suppressor of , the spread of the disease to other organs.

"Based on our findings, we propose that restoring the expression or the function of key suppressors like LIFR could be used to block breast cancer metastasis," said lead investigator Li Ma, Ph.D., assistant professor in MD Anderson's Department of Experimental .

"Lack of clinically proven prognostic markers and therapeutic agents for metastasis are major barriers for eradicating deaths," Ma said. "Although many metastasis-promoting genes have been identified, they have not been translated into clinical practice. The exceptions are the HER2- and VEGF-targeting agents, which have shown measurable but moderate benefit in the clinic."

Only a few genes have been established as metastasis suppressors, Ma said, and many researchers believe that such genes play only a minor role in metastasis.

The investigators in this study, however, found that LIFR is "highly relevant in human tumors." While 94 percent of normal human breast tissues show high LIFR expression, LIFR is downregulated or lost in a significant fraction of patients with in situ (DCIS) or , and loss of LIFR closely correlates with poor clinical outcomes.

Protein works by activating Hippo cascade to throttle YAP

Ma said one of the major findings of the study is that LIFR suppresses both the invasion and colonization steps of metastasis by activating the Hippo kinase cascade that leads to functional inactivation of the transcriptional co-activator YAP.

"The LIFR protein is highly relevant in human cancer because it is down-regulated in about 40 percent of human breast cancers and completely lost in nearly 10 percent," Ma said. "Remarkably, in our study of approximately 1,000 patients, we found that loss of the LIFR protein in non-metastatic stages I to III breast tumors is highly associated with poor metastasis-free, recurrence-free and overall survival outcomes."

Ma noted that this work was regarded by peer reviewers as "a ground-breaking contribution" because it:

  • Challenges the dogma that metastasis-suppressor genes are only a small component of metastasis compared with metastasis-promoting genes;
  • Is the first report of a cell membrane receptor that activates Hippo signaling and has a critical function in cancer; and
  • Might have a significant impact on clinical practice.
Ma said information about LIFR in cancer in the literature is very scarce. But some small studies have reported that LIFR is also lost in colon cancer and liver cancer through a gene-silencing mechanism called hypermethylation.

"There are many directions of research that should be pursued," Ma said. "For example, in order to develop LIFR-based methods of treatment, we must further understand the mechanism of its function and regulation of its expression."

Ma added that her group is generating LIFR conditional knockout mice to determine whether genetic deletion of LIFR in the breast will lead to tumorigenesis and metastasis.

Explore further: New signaling pathway linked to breast cancer metastasis

Related Stories

New signaling pathway linked to breast cancer metastasis

April 2, 2012
Lymph nodes help to fight off infections by producing immune cells and filtering foreign materials from the body, such as bacteria or cancer cells. Thus, one of the first places that cancer cells are found when they leave ...

Protein that functions in normal breast may also contribute to breast cancer metastasis

February 16, 2012
The trefoil factor 3 (TFF3) protein protects and maintains the integrity of the epithelial surface in the normal breast. New research has found that while TFF3 protein expression is higher in well-differentiated low grade ...

TRPM7 protein key to breast cancer metastasis in animal models

August 7, 2012
The protein transient receptor potential melastatin-like 7 (TRPM7) is a critical determinant of breast cancer cell metastasis, according to study results published in Cancer Research, a journal of the American Association ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

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.