- Many types of cancers (including brain, breast, and colon) have significantly less of a protein complex, called the mitochondrial pyruvate carrier (MPC), within them as compared to normal tissue.
- The amount of MPC within a patient’s tumor correlates with patient survival: the less MPC, the more aggressive the cancer.
- Re-introduction of MPC into cancer cells inhibits tumor growth, when cells are grown under conditions commonly used for assessing tumor initiation and metastasis, including after injection into mice.
- Known as the Warburg effect, changes in metabolism have long been known to be important for supporting uncontrolled growth in cancer. MPC, which operates at a critical branch point in carbohydrate metabolism, counteracts the Warburg effect.
- The finding opens new opportunities for developing cancer therapeutics.
Cancer is an unwanted experiment in progress. As the disease advances, tumor cells accumulate mutations, eventually arriving at ones that give them the insidious power to grow uncontrollably and spread. Distinguishing drivers of cancer from benign mutations open opportunities for developing targeted cancer therapies.
Many cancers have significantly less mitochondrial pyruvate carrier within them than normal adult cells. Mice were injected either with control colon cancer cells (dark circles), or colon cancer cells in which mitochondrial pyruvate carrier is re-introduced (white squares). The cancer cells with added MPC form tumors that are significantly smaller, at as little as one-fourth the size.
Credit: Ralph DeBerardinis
This research was funded by grants from the National Institutes of Health and the Nora Eccles Treadwell Foundation
“A Role for the Mitochondrial Pyruvate Carrier as a Repressor of the Warburg Effect and Colon Cancer Growth” online in Molecular Cell on October 30.
Rutter, Schell, and Olson were joined by co-authors Amy Hawkins, Jonathan Van Vranken, and Espen Earl of University of Utah School of Medicine; Lei Jiang, Robert Egnatchik, and Ralph DeBerardinis of UT Southwestern Medical Center; and Jianxin Xie of Cell Signaling Technology, Inc.