LIFR protein suppresses breast cancer metastasis
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 breast cancer metastasis, the spread of the disease to other organs.
"Based on our findings, we propose that restoring the expression or the function of key metastasis 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 Radiation Oncology.
"Lack of clinically proven prognostic markers and therapeutic agents for metastasis are major barriers for eradicating breast cancer 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 ductal carcinoma in situ (DCIS) or invasive breast cancer, 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.
"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.
Journal reference: Nature Medicine
Provided by University of Texas M. D. Anderson Cancer Center
- New signaling pathway linked to breast cancer metastasis Apr 02, 2012 | not rated yet | 0
- Protein that functions in normal breast may also contribute to breast cancer metastasis Feb 16, 2012 | not rated yet | 0
- Experimental agent reduces breast cancer metastasis to bone Nov 03, 2009 | not rated yet | 0
- Tracking breast cancer cells on the move Jun 14, 2012 | not rated yet | 0
- Genes set scene for metastasis Apr 11, 2007 | not rated yet | 0
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
Use of the newer, more expensive intensity-modulated radiotherapy (IMRT) and use of the older conformal radiotherapy (CRT) after surgical removal of all or part of the prostate gland were associated with similar morbidity ...
Cancer 34 minutes ago | not rated yet | 0
Cancer 54 minutes ago | 5 / 5 (1) | 0 |
(HealthDay)—For young adults needing either a chest or abdominopelvic computed tomography (CT), the short-term risk of death from underlying morbidity is greater than the long-term risk of radiation-induced ...
Cancer 2 hours ago | not rated yet | 0
In a new study described in the journal Oncogene, researchers reveal how a key player in cell growth, immunity and the inflammatory response can be transformed into a primary contributor to tumor growth.
Cancer 7 hours ago | not rated yet | 0 |
A new study conducted using extensive medical records of over one million Israeli adolescents before military service shows clearly how exposure to the Israeli sun of young, light-skinned children increases substantially ...
Cancer 9 hours ago | not rated yet | 0
28 minutes ago | not rated yet | 0 |
14 minutes ago | not rated yet | 0 |
41 minutes ago | not rated yet | 0 |
14 minutes ago | not rated yet | 0
Little is known about the effect of physical education (PE) on child weight, but a new study from Cornell University finds that increasing the amount of time that elementary schoolchildren spent in gym class reduces the probability ...
28 minutes ago | not rated yet | 0
Video games that pit players against human-looking characters may be more likely to provoke violent thoughts and words than games where monstrous creatures are the enemy, according to a new study by researchers ...
30 minutes ago | not rated yet | 0