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!
Amputees can learn to control a robotic arm with their minds
28.11.2017 | University of Chicago Medical Center
The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong
Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
14.12.2017 | Health and Medicine
14.12.2017 | Physics and Astronomy
14.12.2017 | Life Sciences