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  • richardmitnick 4:29 pm on May 18, 2017 Permalink | Reply
    Tags: , Lung adenocarcinoma, Lung cancer, , , Wnt signaling proteins   

    From MIT: “Biologists identify key step in lung cancer evolution” 

    MIT News
    MIT Widget

    MIT News

    May 10, 2017
    Anne Trafton

    1
    MIT researchers have found that lung tumors such as this one contain stem-cell-like cells that drive tumor aggression. In this image, those cells are tagged with a green fluorescent protein.
    Image: Tuomas Tammela

    Blocking the transition to a more aggressive state could offer a new treatment strategy.

    [My wife of 53 years died from lung cancer, or the immunotherapy she received to treat it. So this is very personal and difficult for me.]

    Lung adenocarcinoma, an aggressive form of cancer that accounts for about 40 percent of U.S. lung cancer cases, is believed to arise from benign tumors known as adenomas.

    MIT biologists have now identified a major switch that occurs as adenomas transition to adenocarcinomas in a mouse model of lung cancer. They’ve also discovered that blocking this switch prevents the tumors from becoming more aggressive. Drugs that interfere with this switch may thus be useful in treating early-stage lung cancers, the researchers say.

    “Understanding the molecular pathways that get activated as a tumor transitions from a benign state to a malignant one has important implications for treatment. These findings also suggests methods to prevent or interfere with the onset of advanced disease,” says Tyler Jacks, director of MIT’s Koch Institute for Integrative Cancer Research and the study’s senior author.

    The switch occurs when a small percentage of cells in the tumor begin acting like stem cells, allowing them to give rise to unlimited populations of new cancer cells.

    “It seems that the stem cells are the engine of tumor growth. They’re endowed with very robust proliferative potential, and they give rise to other cancer cells and also to more stem-like cells,” says Tuomas Tammela, a postdoc at the Koch Institute and lead author of the paper, which appears in the May 10 online edition of Nature.

    Tumor stem cells

    In this study, the researchers focused on the role of a cell signaling pathway known as Wnt. This pathway is usually turned on only during embryonic development, but it is also active in small populations of adult stem cells that can regenerate specific tissues such as the lining of the intestine.

    One of the Wnt pathway’s major roles is maintaining cells in a stem-cell-like state, so the MIT team suspected that Wnt might be involved in the rapid proliferation that occurs when early-stage tumors become adenocarcinomas.

    The researchers explored this question in mice that are genetically programmed to develop lung adenomas that usually progress to adenocarcinoma. In these mice, they found that Wnt signaling is not active in adenomas, but during the transition, about 5 to 10 percent of the tumor cells turn on the Wnt pathway. These cells then act as an endless pool of new cancer cells.

    In addition, about 30 to 40 percent of the tumor cells begin to produce chemical signals that create a “niche,” a local environment that is necessary to maintain cells in a stem-cell-like state.

    “If you take a stem cell out of that microenvironment, it rapidly loses its properties of stem-ness,” Tammela says. “You have one cell type that forms the niche, and then you have another cell type that’s receiving the niche cues and behaves like a stem cell.”

    While Wnt has been found to drive tumor formation in some other cancers, including colon cancer, this study points to a new kind of role for it in lung cancer and possibly other cancers such as pancreatic cancer.

    “What’s new about this finding is that the pathway is not a driver, but it modifies the characteristics of the cancer cells. It qualitatively changes the way cancer cells behave,” Tammela says.

    “It’s a very nice paper that points to the influence of the microenvironment in tumor growth and shows that the microenvironment includes factors secreted by a subset of tumor cells,” says Frederic de Sauvage, vice president for molecular oncology research at Genentech, who was not involved in the study.

    Targeting Wnt

    When the researchers gave the mice a drug that interferes with Wnt proteins, they found that the tumors stopped growing, and the mice lived 50 percent longer. Furthermore, when these treated tumor cells were implanted into another animal, they failed to generate new tumors.

    The researchers also analyzed human lung adenocarcinoma samples and found that 70 percent of the tumors showed Wnt activation and 80 percent had niche cells that stimulate Wnt activity. These findings suggest it could be worthwhile to test Wnt inhibitors in early-stage lung cancer patients, the researchers say.

    They are also working on ways to deliver Wnt inhibitors in a more targeted fashion, to avoid some of the side effects caused by the drugs. Another possible way to avoid side effects may be to develop more specific inhibitors that target only the Wnt proteins that are active in lung adenocarcinomas. The Wnt inhibitor that the researchers used in this study, which is now in clinical trials to treat other types of cancer, targets all 19 of the Wnt proteins.

    The research was funded by the Janssen Pharmaceuticals-Koch Institute Transcend Program, the Lung Cancer Research Foundation, the Howard Hughes Medical Institute, and the Cancer Center Support grant from the National Cancer Institute.

    See the full article here .
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  • richardmitnick 9:48 am on December 5, 2016 Permalink | Reply
    Tags: , , Breakthrough Prizes, , Roeland Nusse, , , Wnt signaling proteins   

    From Stanford: “Roeland Nusse wins $3 million Breakthrough Prize” 

    Stanford University Name
    Stanford University

    12.4.16
    Krista Conger

    1
    Roeland Nusse was awarded the 2017 Breakthrough Prize in life sciences for his contributions to the understanding a signaling molecule called Wnt. Norbert von der Groeben

    The developmental biologist was honored for helping to decode how Wnt signaling proteins affect embryonic development, cancer and the activity of tissue-specific adult stem cells that repair damage after injury or disease.

    Roeland Nusse, PhD, the Virginia and Daniel K. Ludwig Professor in Cancer Research and a Howard Hughes Medical Institute investigator, was honored this evenng with a 2017 Breakthrough Prize in life sciences.

    Nusse was awarded the $3 million prize for his contributions to the understanding of how a signaling molecule called Wnt affects normal development, cancer and the functions of adult stem cells in many tissues throughout the body.

    “This is a complete surprise,” said Nusse, who is professor and chair of developmental biology. “My gratitude goes out to many people — my past and present postdoctoral scholars and graduate students and my former mentors have all contributed to the success of my research. The research and collaborative environment at Stanford and the long-term support from the Howard Hughes Medical Institute have also been fantastic. I see this award as a great honor for the entire community.”

    The Breakthrough Prizes, initiated in 2013, honor paradigm-shifting research and discovery in the fields of life sciences, fundamental physics and mathematics. In total, about $25 million was awarded at this year’s ceremony, a black-tie, red-carpet affair at the NASA Ames Research Center in Mountain View. The event was hosted by actor Morgan Freeman. The Grammy Award-winning pop star Alicia Keys provided entertainment.

    “Roel’s pioneering work has provided deep insights into an essential molecular signaling pathway that controls normal embryonic development and adult tissue repair, and that contributes to cancer when it is not properly regulated. His work has served as a model for many others in our field and accelerated further studies of these critical processes,” said Stanford President Marc Tessier-Lavigne, PhD. “We are grateful that the Breakthrough Prize recognizes the work of scientific leaders who are inspiring others to pursue discovery that is truly transformative, benefiting all of humanity.”

    Nusse’s interest in Wnt began in the 1980s as a postdoctoral scholar in the laboratory of Harold Varmus, MD, who was then on the faculty of UC-San Francisco. In 1982, Nusse discovered the Wnt1 gene, which was abnormally activated in a mouse model of breast cancer. He subsequently discovered that members of the Wnt family of proteins also play critical roles in embryonic development, cell differentiation and tissue regeneration.

    “Roel has devoted his career to identifying one of the major signaling molecules in embryonic development, and clarifying its role in cancer development and in tissue regeneration,” said Lloyd Minor, MD, dean of the School of Medicine. “The importance of Wnt signaling in these processes cannot be overestimated. His work has been the foundation of much of modern developmental biology, and we are very proud of his contributions.”

    Nusse’s more recent work has focused on understanding how Wnt family members control the function of adult stem cells in response to injury or disease. In 1996, he identified the cell-surface receptor to which Wnt proteins bind to control cells’ functions, and in 2002 he was the first to purify Wnt proteins — an essential step to understanding how they work at a molecular level.

    “My work has shifted significantly over the years due to the influence of my Stanford colleagues, although it has always been focused on Wnt,” said Nusse. “When I arrived at Stanford, I was studying the involvement of the Wnt proteins in mouse development and cancer. I then switched to fruit flies, and then to the study of adult stem cells. Stanford has supported me during this evolution of my research career.”

    Nusse’s lab is currently devoted to understanding how Wnt signaling affects the function of adult stem cells in the liver to help the organ heal after injury, as well as what role Wnt signaling might play in the development of liver cancer.

    “The Breakthrough Prizes are a sign of the times,” said Nusse. “Together with the recently announced Chan Zuckerberg Initiative, they show how the wealth of Silicon Valley is now making an impact not just in the field of computer science, but also in biomedical fields. This is very exciting.”

    Nusse is a member of the Ludwig Center for Cancer Stem Cell Research and Medicine at Stanford, of the Stanford Cancer Institute and of the Stanford Institute for Stem Cell Biology and Regenerative Medicine. He was awarded the Peter Debye Prize from the University of Maastricht in 2000. He is a member of the U.S. National Academy of Sciences, the European Molecular Biology Organization and the Royal Dutch Academy of Sciences. He is also a fellow of the American Academy of Arts and Sciences.

    In all, seven $3 million Breakthrough Prizes — five in the life sciences, one in fundamental physics and one in mathematics — were awarded to 12 recipients. In addition, a special Breakthrough Prize in fundamental physics was awarded to the more than one thousand researchers who proved the existence of gravitational waves in February of 2016.

    Probing for dark matter

    2
    Peter Graham. No image credit

    In addition, three $100,000 New Horizons in Physics Prizes were awarded at the ceremony. Peter Graham, PhD, an assistant professor of physics at Stanford, shared one of them with Asimina Arvanitaki of the Perimeter Institute in Ontario, Canada, and Surjeet Rajendran of the University of California-Berkeley, for “pioneering a wide range of new experimental probes of fundamental physics.”

    Graham earned a PhD at Stanford and completed postdoctoral studies at the Stanford Institute for Theoretical Physics before joining the Stanford faculty in 2010. In 2014, he received an Early Career Award from the Department of Energy.

    Graham has developed new experiments to detect particles known as dark matter, which physicists have reason to believe exist but haven’t yet been able to detect. Physicists have theorized about what dark matter might be, and based on that work have designed experiments to detect those theorized particles. However, those experiments would miss one possible variant of what dark matter might be, known as an axion.

    “It was a scary scenario that this might be what dark matter is and our current experiments wouldn’t detect it,” Graham said.

    Graham designed new experimental approaches that would detect axions if they turn out to be what make up dark matter. “This prize is a huge honor,” Graham said. “It’s great to get recognition from the community for this new direction; it will really help this emerging field.”

    Three $100,000 New Horizons in Mathematics prizes were also awarded at the Breakthrough Prize ceremony.

    In addition, two teenagers — one from Peru and one from Singapore — each won the 2017 Breakthrough Junior Challenge. They will each receive $400,000 in educational prizes.

    The Breakthrough Prizes are funded by grants from the Brin Wojcicki Foundation, established by Google founder Sergey Brin and 23andMe founder Anne Wojcicki; Mark Zuckerberg’s fund at the Silicon Valley Community Foundation; Alibaba founder Jack Ma’s foundation; and DST Global founder Yuri Milner’s foundation. Recipients are chosen by committees comprised of prior prizewinners.

    Amy Adams, director for science communications at the Stanford News Service, contributed to this article.

    See the full article here .

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