In human cancers, a proto-oncogene called MYC is often mutated or overexpressed. As a transcription factor, MYC protein affects the expression of multiple genes and regulates cell differentiation and proliferation; when it becomes abnormal, it triggers a chain reaction that causes abnormal cell proliferation. Tumor cells that highly express MYC not only grow out of control, but also metabolize differently from normal cells and are particularly dependent on certain nutrients.
In a new study in Nature Metabolism, scientists found that breast cancer cells that highly express Myc are critically dependent on vitamin B5 for growth and survival, and this dependence can serve as a potential therapeutic target.
The researchers simulated the molecular characteristics of human cancer and constructed a group of tumor mice. These tumors contained cancer cells with high expression of Myc and cancer cells with low expression of Myc. Similarly, the researchers transplanted tumor tissue from breast cancer patients into mice, which also contained areas of high MYC expression and areas of low MYC expression.
Using mass spectrometry imaging, the researchers noticed that within the tumors of these mice, areas of high Myc expression were always associated with vitamin B5 metabolism. The researchers further observed this association in biopsy samples from breast cancer patients.
Vitamin B5, also known as pantothenic acid, is named for its wide distribution in plants and animals, and its active form is Coenzyme A, which is involved in many metabolic pathways such as lipid metabolism and helps cells produce more energy and substances for cell growth.
In cells with high expression of Myc, they have more vitamin transporter SLC5A6, thus helping the cells to supplement more vitamin B5. When the researchers loaded cells with low Myc expression with more of the vitamin transporter SLC5A6, the cells grew faster as more vitamin B5 entered the cells.
Since these cancer cells love to "supplement" vitamin B5 so much, will they also be inhibited first when lacking this vitamin? The researchers fed the mice with the above-mentioned tumors a diet lacking vitamin B5 and found that the growth rate of the tumors was significantly slower than that of mice fed a standard diet.
Restricting the intake of pantothenic acid (PA) in mice inhibits tumor growth
Although this study links vitamin B5 to tumor growth, clinical treatment cannot simply limit the intake of vitamin B5 in cancer patients, because vitamin B5 is inseparable from normal body functions and is also important for the immune system to fight tumors. Importantly, a clever balance is needed to limit the tumor's access to vitamin B5.
The researchers pointed out that follow-up work to understand how vitamin levels affect treatment outcomes, or to use vitamin B5 metabolism levels as a biomarker to characterize a patient's tumor type and what kind of treatment they respond to, will guide us to find new methods. Selectively weaken tumors without affecting the immune system.