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Researchers have identified a strategy that can potentially control MAPK4-promoted growth in triple-negative breast cancer and other cancers
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New Protein Target to Suppress Triple-Negative Breast Cancer Growth

Blocking proteins that activate the AGC group of enzymes has been shown to have tumor-suppressing effects

Baylor College of Medicine
Published:Aug 03, 2023
|2 min read
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In 2022, a team of researchers at Baylor College of Medicine (Baylor) discovered that a little-known enzyme, called MAPK4, is involved in the growth of triple-negative breast cancer (TNBC) and its resistance to certain therapies. Looking into the details of this novel role of MAPK4, the researchers have now identified a strategy that can potentially control MAPK4-promoted growth in TNBC and other cancers. The study, published in PLOS Biology, opens new options for treating this devastating disease.

“Some cancers depend on MAPK4 for their growth, and our team studies cellular processes or pathways that participate in MAPK4-induced cancer growth,” said corresponding author Feng Yang, PhD, associate professor of pathology and immunology and of molecular and cellular biology. He also is a member of the Dan L Duncan Comprehensive Cancer Center at Baylor.

Yang and his team knew that in some TNBC cases, MAPK4 activates an enzyme called AKT, which promotes cancer growth. They also knew that in the same cells, another enzyme called PDK1 can also promote cancer growth by activating both AKT and a series of other enzymes of the protein A, G, and C (AGC) family kinases. This PDK1-mediated activation of AGC enzymes mostly depends on the amount of PDK1 in the cell.

In this study, the team discovered that MAPK4 and PDK1 are in some way co-dependent in their tumor-promoting actions, and this led to a novel idea on how to treat these cancers. Working with TNBC cells in the lab, the researchers found that, besides directly activating AKT, MAPK4 also enhances the production of PDK1in cells, which, in turn, promotes tumor growth. “We found that MAPK4 can activate both AKT and PDK1, which then work together enhancing cancer growth and resistance to therapy,” said Yang. “Eliminating MAPK4 in cells in the lab inhibited both of its actions on AKT and PDK1 and reduced tumor growth.”

However, there are no drugs that specifically block MAPK4 that could be tested to reduce tumor growth. Instead, Yang and colleagues explored an alternative approach. “We showed that blocking both AKT and PDK1 effectively repressed MAPK4-induced cancer cell growth, suggesting a potential therapeutic strategy to treat MAPK4-dependent cancers, such as a subset of TNBC, prostate, and lung cancer.”

“In this study, we have not only advanced our understanding of the molecular mechanism underlying the tumor-promoting activity of MAPK4, we also have found a potential novel therapeutic approach for human cancers,” said Yang.

- This press release was originally published on the Baylor College of Medicine website