Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Potentially targetable signaling pathway generates slowly proliferating, chemo-resistant cancer cells

12.01.2015

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.

Follow us: Cancer Research Catalyst http://blog.aacr.org; Twitter @AACR; and Facebook http://www.facebook.com/aacr.org

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.AACR.org.

Jeremy Moore | EurekAlert!

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

Im Focus: Using graphene to create quantum bits

In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.

In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

Physicists discover mechanism behind granular capillary effect

24.05.2017 | Physics and Astronomy

Measured for the first time: Direction of light waves changed by quantum effect

24.05.2017 | Physics and Astronomy

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>