Inducing metabolic catastrophe in cancer cells

August 31, 2015
Eliminating HK2 (shown here), which is a key enzyme for glucose metabolism, may be a way to prevent cancer cells from surviving, according to a new study in JCB. Credit: Xia et al., 2015

A study published in The Journal of Cell Biology describes a way to force cancer cells to destroy a key metabolic enzyme they need to survive.

Cancer cells survive the stressful environment inside a tumor in part through autophagy, the controlled digestion and recycling of damaged components. However, blocking the process doesn't kill , so researchers have been looking for a way to make cells vulnerable to autophagy shutdown.

Researchers at Harvard Medical School in Boston used an cell line that is resistant to the autophagy inhibitor spautin-1 or an upgraded version of this molecule. After screening more than 8,200 compounds, they found that quizartinib was the most effective at enhancing the cells' vulnerability to either of the autophagy blockers. Quizartinib inhibits FLT3, an enzyme that is important for the normal development of and a validated target for (AML). The drug is currently in clinical trial for treatment of AML, but its value beyond has not been well explored.

The team found that quizartinib and the improved version of spautin-1 killed from a variety of cell lines while leaving noncancerous cells unscathed. Treating cancer cells with quizartinib alone inhibited an important metabolic pathway, glycolysis, and activated macroautophagy, the best known type of autophagy in which the cell digests a large portion of its contents. In contrast, cells that received both compounds couldn't initiate macroautophagy, but they switched on chaperone-mediated autophagy, a selective form of the process that eliminates individual molecules.

One of its targets was the enzyme Hexokinase2 (HK2), which is crucial for glucose metabolism and is often overexpressed in cancer cells. By eliminating HK2, quizartinib and the autophagy inhibitor may prevent cancer cells from metabolizing absorbed glucose and mobilizing stored nutrients, thereby triggering cancer cell death. The study provides evidence that combining an FLT3 inhibitor with an autophagy blocker could be a new way to treat cancer.

Explore further: Protein induces self-destruction in cancer cells

More information: Xia, H.-g., et al. 2015. J. Cell Biol. dx.doi.org/10.1083/jcb.201503044

Related Stories

Protein induces self-destruction in cancer cells

January 21, 2015
The role of a phosphatase protein in promoting the self-destruction of healthy cells and the progression of ovarian cancer has been identified by A*STAR researchers. Known to be overexpressed in cancer cells, the protein, ...

Zombie cancer cells eat themselves to live

April 5, 2014
A University of Colorado Cancer Center study recently published in the journal Cell Reports and presented today at the American Association for Cancer Research (AACR) Annual Conference 2014 shows that the cellular process ...

New drug squashes cancer's last-ditch efforts to survive

June 25, 2015
As a tumor grows, its cancerous cells ramp up an energy-harvesting process to support its hasty development. This process, called autophagy, is normally used by a cell to recycle damaged organelles and proteins, but is also ...

Improved effectiveness of chemotherapy for cancer

August 15, 2013
Cancer cells often develop defence mechanisms which enable them to survive chemotherapy. A group of researchers from the Institutes of Pharmacology and Pathology in Bern present new solutions for preventing the development ...

Researchers find new target for kidney cancer therapy

November 10, 2014
Cincinnati Cancer Center (CCC) researchers have discovered that a membrane channel, Transient Receptor Potential Melastatin 3, or TRPM3, promotes growth of kidney cancer tumors, and targeting this channel therapeutically ...

Recommended for you

New therapeutic approach for difficult-to-treat subtype of ovarian cancer identified

July 24, 2017
A potential new therapeutic strategy for a difficult-to-treat form of ovarian cancer has been discovered by Wistar scientists. The findings were published online in Nature Cell Biology.

Immune cells the missing ingredient in new bladder cancer treatment

July 24, 2017
New research offers a possible explanation for why a new type of cancer treatment hasn't been working as expected against bladder cancer.

Anti-cancer chemotherapeutic agent inhibits glioblastoma growth and radiation resistance

July 24, 2017
Glioblastoma is a primary brain tumor with dismal survival rates, even after treatment with surgery, chemotherapy and radiation. A small subpopulation of tumor cells—glioma stem cells—is responsible for glioblastoma's ...

No dye: Cancer patients' gray hair darkened on immune drugs

July 21, 2017
Cancer patients' gray hair unexpectedly turned youthfully dark while taking novel drugs, and it has doctors scratching their heads.

Shooting the achilles heel of nervous system cancers

July 20, 2017
Virtually all cancer treatments used today also damage normal cells, causing the toxic side effects associated with cancer treatment. A cooperative research team led by researchers at Dartmouth's Norris Cotton Cancer Center ...

Molecular changes with age in normal breast tissue are linked to cancer-related changes

July 20, 2017
Several known factors are associated with a higher risk of breast cancer including increasing age, being overweight after menopause, alcohol intake, and family history. However, the underlying biologic mechanisms through ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.