Nav: Home

Genetic 'whodunnit' for cancer gene solved

November 08, 2018

LA JOLLA--(November 8, 2018) Long thought to suppress cancer by slowing cellular metabolism, the protein complex AMPK also seemed to help some tumors grow, confounding researchers. Now, Salk Institute researchers have solved the long-standing mystery around why AMPK can both hinder and help cancer.

The lab of Salk Professor Reuben Shaw showed that late-stage cancers can trigger AMPK's cellular recycling signal to cannibalize pieces of the cell, supplying large lung tumors with the nutrients they need to grow. The work, which appeared in Cell Metabolism on November 8, 2018, suggests that blocking AMPK in some conditions could stop the growth of advanced tumors in the most common type of lung cancer.

"Our study shows that the same dysfunction in a genetic circuit that causes non-small-cell lung cancer to begin with is necessary for more mature tumor cells to survive when they don't have enough nutrients," says Shaw, director of the Salk Cancer Center and the paper's senior author. "It's exciting because not only does it solve a genetic 'whodunnit,' but it also points to a potential new therapeutic target for a cancer that is often diagnosed very late."

AMPK acts as a fuel gauge for the cell, overseeing energy input and output to keep the cell running smoothly. Similar to a car sensor flashing a low-gas signal or turning off a vehicle's AC to save energy, AMPK slows down cell growth and changes the cell's metabolism if the cell's fuel (nutrients) is low. Previously, Shaw discovered that AMPK could halt tumors' revved-up metabolism, as well as restore normal function to the liver and other tissues in diabetics.

But the Shaw lab's new work suggests that AMPK actually helps large tumors grow. In the current study, the team observed groups of mice with and without the AMPK fuel gauge to see how tumors developed.

"We found that tumors grew much more slowly when AMPK was not present," says Research Associate Lillian Eichner, the paper's first author. "That means that AMPK is not always functioning as a tumor suppressor, as we originally thought."

The team analyzed which genes in tumor cells from the same mouse models were being activated under various conditions. One gene that was particularly active was Tfe3, which is known to activate cellular recycling. It turned out that when tumors became large enough that cells in the middle were too far from easy access to nutrients, AMPK signaled Tfe3 to initiate recycling of cellular materials as nutrients--effectively cannibalizing pieces of the cell--for the tumor to use.

"Previously we were focused on how we could activate AMPK," says Eichner. "Now that we've identified this mechanism, we can shift to how to inhibit it in certain cancers."

Shaw, who holds the William R. Brody Chair, adds, "We're excited because more advanced tumors seem to rely on AMPK to survive, and understanding this mechanism means we may be able to treat them."
-end-
Other authors included Sonja N. Brun, Sébastien Herzig, Nathan P. Young, Stephanie D. Curtis, David B. Shackelford, Maxim N. Shokhirev, Mathias Leblanc, Liliana I. Vera, Amanda Hutchins, Debbie S. Ross and Robert U. Svensson.?

The work was funded by the National Institutes of Health (R35CA220538, P01CA120964), the Samuel Waxman Cancer Research Foundation, The Leona M. and Harry B. Helmsley Charitable Trust (grant #2012-PG- MED002) and the American Cancer Society (ACS#124183-PF-13-023-01-CSM)(PF-15-037-01-DMC).

About the Salk Institute for Biological Studies:

Every cure has a starting point. The Salk Institute embodies Jonas Salk's mission to dare to make dreams into reality. Its internationally renowned and award-winning scientists explore the very foundations of life, seeking new understandings in neuroscience, genetics, immunology, plant biology and more. The Institute is an independent nonprofit organization and architectural landmark: small by choice, intimate by nature and fearless in the face of any challenge. Be it cancer or Alzheimer's, aging or diabetes, Salk is where cures begin. Learn more at: salk.edu.

Salk Institute

Related Cancer Articles:

Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
Cancer genomics continued: Triple negative breast cancer and cancer immunotherapy
Continuing PLOS Medicine's special issue on cancer genomics, Christos Hatzis of Yale University, New Haven, Conn., USA and colleagues describe a new subtype of triple negative breast cancer that may be more amenable to treatment than other cases of this difficult-to-treat disease.
Metabolite that promotes cancer cell transformation and colorectal cancer spread identified
Osaka University researchers revealed that the metabolite D-2-hydroxyglurate (D-2HG) promotes epithelial-mesenchymal transition of colorectal cancer cells, leading them to develop features of lower adherence to neighboring cells, increased invasiveness, and greater likelihood of metastatic spread.
UH Cancer Center researcher finds new driver of an aggressive form of brain cancer
University of Hawai'i Cancer Center researchers have identified an essential driver of tumor cell invasion in glioblastoma, the most aggressive form of brain cancer that can occur at any age.
UH Cancer Center researchers develop algorithm to find precise cancer treatments
University of Hawai'i Cancer Center researchers developed a computational algorithm to analyze 'Big Data' obtained from tumor samples to better understand and treat cancer.
New analytical technology to quantify anti-cancer drugs inside cancer cells
University of Oklahoma researchers will apply a new analytical technology that could ultimately provide a powerful tool for improved treatment of cancer patients in Oklahoma and beyond.
Radiotherapy for lung cancer patients is linked to increased risk of non-cancer deaths
Researchers have found that treating patients who have early stage non-small cell lung cancer with a type of radiotherapy called stereotactic body radiation therapy is associated with a small but increased risk of death from causes other than cancer.
Cancer expert says public health and prevention measures are key to defeating cancer
Is investment in research to develop new treatments the best approach to controlling cancer?
UI Cancer Center, Governors State to address cancer disparities in south suburbs
The University of Illinois Cancer Center and Governors State University have received a joint four-year, $1.5 million grant from the National Cancer Institute to help both institutions conduct community-based research to reduce cancer-related health disparities in Chicago's south suburbs.
Leading cancer research organizations to host international cancer immunotherapy conference
The Cancer Research Institute, the Association for Cancer Immunotherapy, the European Academy of Tumor Immunology, and the American Association for Cancer Research will join forces to sponsor the first International Cancer Immunotherapy Conference at the Sheraton New York Times Square Hotel in New York, Sept.

Related Cancer Reading:

The Emperor of All Maladies: A Biography of Cancer
by Siddhartha Mukherjee (Author)

The Cancer-Fighting Kitchen, Second Edition: Nourishing, Big-Flavor Recipes for Cancer Treatment and Recovery
by Rebecca Katz (Author), Mat Edelson (Author)

Anticancer: A New Way of Life
by David Servan-Schreiber MD PhD (Author)

The Truth about Cancer: What You Need to Know about Cancer's History, Treatment, and Prevention
by Ty M. Bollinger (Author)

F*ck Cancer: A totally inappropriate self-affirming adult coloring book (Totally Inappropriate Series) (Volume 4)
by Jen Meyers (Author)

Chris Beat Cancer: A Comprehensive Plan for Healing Naturally
by Chris Wark (Author)

The Metabolic Approach to Cancer: Integrating Deep Nutrition, the Ketogenic Diet, and Nontoxic Bio-Individualized Therapies
by Dr. Nasha Winters ND FABNO L.Ac Dipl.OM (Author), Jess Higgins Kelley MNT (Author), Kelly Turner (Foreword)

How to Starve Cancer
by Jane McLelland (Author)

Keto for Cancer: Ketogenic Metabolic Therapy as a Targeted Nutritional Strategy
by Miriam Kalamian EdM MS CNS (Author), Thomas N. Seyfried (Foreword)

The Cancer Revolution: A Groundbreaking Program to Reverse and Prevent Cancer
by Leigh Erin Connealy (Author)

Best Science Podcasts 2018

We have hand picked the best science podcasts for 2018. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Unintended Consequences
Human innovation has transformed the way we live, often for the better. But as our technologies grow more powerful, so do their consequences. This hour, TED speakers explore technology's dark side. Guests include writer and artist James Bridle, historians Yuval Noah Harari and Edward Tenner, internet security strategist Yasmin Green, and journalist Kashmir Hill.
Now Playing: Science for the People

#499 Technology, Work and The Future (Rebroadcast)
This week, we're thinking about how rapidly advancing technology will change our future, our work, and our well-being. We speak to Richard and Daniel Susskind about their book "The Future of Professions: How Technology Will Transform the Work of Human Experts" about the impacts technology may have on professional work. And Nicholas Agar comes on to talk about his book "The Sceptical Optimist" and the ways new technologies will affect our perceptions and well-being.