▎ WuXi AppTec content team editor
The advent of a variety of anti-cancer therapies has made cancer no longer a terminal disease. However, once cancer cells begin to metastasize to other tissues or organs in the body, they can quickly become difficult to treat. In fact, metastasis is the leading cause of death from cancer.
From primary tumors to metastatic tumors, how do cancer cells gain the ability to metastasize? Scientists believe that finding the answer to this question will lead to new ways to stop cancer cells from spreading. Recently, scientists at Weill Cornell Medicine have made a progress, and the results of the study are published in Nature-Metabolism.
The study focused on the metabolic changes that cancer cells undergo, as changes in metabolic pathways are thought to be a key strategy for cancer cells to acquire the ability to metastasize. Through a mouse model of lung metastasis of breast cancer, the researchers found that the dysregulation of propionate metabolism, a metabolic pathway when cancer cells digest certain fatty acids and protein components, increases the metastasis potential of cancer cells.
In this process, metastatic cancer cells inhibit the activity of MCEE, a key enzyme in propionate's metabolic pathway, leading to a continuous accumulation of metabolic byproduct methylmalonic acid (MMA) within cells and within tumors.
Some previous studies have pointed out that MMA can alter gene expression in cancer cells, prompting cancer cells to exhibit aggressive properties. The study found that metastatic cancer cells are very "heavy" MMA, on the one hand, not only using MMA produced by foreign sources (such as other healthy cells), but also producing MMA themselves; on the other hand, tumor cells that are still "honestly" in place do not have MMA upregulation, and only the MMA increases in cancer cells that may form metastases.
Thus, these results mean that cancer cells form a positive cycle with MMA, pushing the disease in a more aggressive and more metastatic direction.
Consistent with the findings in a mouse model of breast cancer, the researchers also found in human breast cancer cells that MMA levels were higher in the most aggressive triple-negative breast cancer cell lines than in other cell lines that did not metastases.
Image credit: 123RF
The research team concluded in the abstract of the paper: "Our study proposes that dysbolic propionate metabolism has an important contribution to cancer and is justified as a potential target for the treatment of cancer metastasis." ”
Although the study was clustered around various models of breast cancer, the researchers speculate that there may be similar mechanisms in other types of cancer cells, and they hope to find a way to crack it.
Dr. John Blenis, corresponding author of the study paper, points out: "Metastasis accounts for about 80% to 90% of cancer-related mortality, and if we can predict when a patient may develop a metastatic tumor, or treat metastatic tumors modulated along the way, then we may have a very effective new treatment." ”
Resources:
[2] Tumors change their metabolism to spread more effectively. Retrieved Apr. 19, 2022 from https://news.cornell.edu/stories/2022/04/tumors-change-their-metabolism-spread-more-effectively
More recommendations
Click "Watching" and go again