Researchers discovered that the same cellular pathway that has been shown to be involved with the spread of colorectal cancer is also responsible for providing lung cancer with an enhanced ability to infiltrate and colonize other organs without delay and with little need to adapt to its new environment.
This is a dramatic departure from other cancers, like breast cancer, in which recurrences tend to emerge following years of remission, suggesting that such cancer cells initially lack – and need time to acquire – the characteristics and ability to spread to other organs.
The investigators hypothesized that because not all lung tumors have spread before diagnosis and removal, metastasis may depend on some added feature beyond the mutations that initiate these tumors.
Researchers used bioinformatics to interrogate large collections of lung tumor samples. They found that the WNT cell-signaling pathway was the only one out of the six pathways tested that was hyperactive in lung tumors that went on to metastasize and was normal in those that did not spread. They also observed that WNT hyperactivity was associated with aggressive biological tumor characteristics and poor clinical outcome, suggesting that cancer metastasis is linked to poor survival.
"Mutations that activate the WNT pathway are a common cause of colon cancer, but lung tumors are initiated by mutations in other genes so we were surprised that a hyperactive WNT pathway would be responsible for metastasis in lung cancer," said the study's senior author Joan Massagué, PhD, Chair of the Cancer Biology and Genetics Program at MSKCC and a Howard Hughes Medical Institute investigator.
This finding was confirmed with additional experiments in mice that showed that lung cancer cells with tumor-initiating mutations in the genes KRAS and EGFR also depended on a hyperactive WNT pathway for metastasis. The researchers went on to find two genes – HOXB9 and LEF1 – that are activated by WNT and enhance the ability of lung cancer cells to swiftly invade and reinitiate tumor growth. These are functions that cancer cells need in order to conquer other organs and that are being enabled by the WNT pathway in the primary tumor.
"Our findings suggest that using treatments that target the WNT pathway may help prevent lung cancer from repeatedly seeding itself throughout the vital organs of patients at risk for metastasis," said Dr. Massagué.
The following investigators at MSKCC contributed to this research: Don X. Nguyen, Anne C. Chiang, Xiang H. F. Zhang, Juliet Y. Kim, Mark G. Kris, Marc Ladanyi, and the late William L. Gerald.
The work was supported by grants from the National Institutes of Health, the Damon Runyon Cancer Research Foundation, the American Society of Clinical Oncology, the Hearst Foundation, and the Alan and Sandra Gerry Metastasis Research Initiative.
Memorial Sloan-Kettering Cancer Center is the world's oldest and largest private institution devoted to prevention, patient care, research, and education in cancer. Our scientists and clinicians generate innovative approaches to better understand, diagnose, and treat cancer. Our specialists are leaders in biomedical research and in translating the latest research to advance the standard of cancer care worldwide. For more information, go to www.mskcc.org.
Esther Napolitano | EurekAlert!
Rutgers-led innovation could spur faster, cheaper, nano-based manufacturing
14.02.2018 | Rutgers University
New study from the University of Halle: How climate change alters plant growth
12.01.2018 | Martin-Luther-Universität Halle-Wittenberg
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.
In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...
19.03.2018 | Event News
16.03.2018 | Event News
13.03.2018 | Event News
22.03.2018 | Trade Fair News
22.03.2018 | Earth Sciences
22.03.2018 | Earth Sciences