A signaling pathway responsible for the generation of slowly proliferating cancer cells, which are hard to eradicate with current treatments and thought to be a cause of subsequent disease relapse, has been reported in a Rapid Impact study published in Molecular Cancer Research, a journal of the American Association for Cancer Research.
"We have identified a new pathway in which well-studied signaling molecules string together to regulate cell proliferation," said Sridhar Ramaswamy, MD, an associate professor of medicine at Massachusetts General Hospital Cancer Center and Harvard Medical School in Boston. "Since a number of these molecules are under intensive study as therapeutic targets for various cancer types, we are currently designing strategies to target this pathway in animal models in order to better clarify the potential clinical implications of these findings.
"All cancers contain some cells that are rapidly proliferating and many that proliferate only very slowly," explained Ramaswamy, who is also an associate member of the Broad Institute and the Harvard Stem Cell Institute. "Most cancer treatments target rapidly dividing cancer cells but leave the slowly dividing ones unharmed and still capable of causing disease recurrence after the initial treatment. Our goal has been to understand how these slow proliferators are produced in order to devise ways to eliminate them."
When cancer cells growing in the laboratory divide, they usually produce two daughter cells that have the same rate of proliferation, but sometimes one daughter cell proliferates at a much slower pace than the other.
Ramaswamy and colleagues have been investigating why cancer cells undergo this type of asymmetric cell division for a number of years. In a previously published study, they found that if a cancer cell asymmetrically suppresses expression of a protein called AKT right before dividing, it produces two daughter cells: one that has normal levels of AKT protein and proliferates rapidly like the parent cell, and one that has low levels of AKT and proliferates slowly.
They also detected these rare cancer cells with low levels of AKT in breast cancer patients and found that these cells were highly resistant to the combination chemotherapy being used to treat the patients.
In this new study, the researchers used a number of molecular biology techniques to investigate how cancer cells dividing in the laboratory produce daughter cells with different levels of AKT. They found that decreased signaling through beta1-integrin, a molecule found on the surface of most cancer cells, decreased the activity of the signaling molecule FAK. This, in turn, increased the activity of a complex of signaling molecules called mTORC2, which led to suppression of AKT1 protein levels by a molecule called TTC3 and the proteasome complex.
"Prior to these studies, we thought that asymmetric suppression of AKT might just relate to random fluctuations in protein levels during cell division," said Ramaswamy. "We discovered that this is not the case; it is actually regulated by a potentially targetable signaling pathway, which may offer new avenues for reducing the proliferative heterogeneity within tumors for therapeutic effect."
The study was supported by funds from Stand Up To Cancer, the National Cancer Institute, the Howard Hughes Medical Institute, Susan G. Komen, the Prostate Cancer Foundation, CNPq (the National Council for Scientific and Technological Development in Brazil), and Instituto de Salud Carlos III in Spain. Ramaswamy declares no conflicts of interest.
For AACR information, visit Fast Facts
About the American Association for Cancer Research
Founded in 1907, the American Association for Cancer Research (AACR) is the world's oldest and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR membership includes more than 33,000 laboratory, translational, and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in 101 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis, and treatment of cancer by annually convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with over 18,000 attendees. In addition, the AACR publishes eight peer-reviewed scientific journals and a magazine for cancer survivors, patients, and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review, grants administration, and scientific oversight of team science and individual grants in cancer research that have the potential for near-term patient benefit. The AACR actively communicates with legislators and policymakers about the value of cancer research and related biomedical science in saving lives from cancer. For more information about the AACR, visit http://www.
Jeremy Moore | EurekAlert!
New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University
Penn study identifies new malaria parasites in wild bonobos
21.11.2017 | University of Pennsylvania School of Medicine
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences