May 1, 2025 | Austin, Minn. — Roughly 1 in 8 women will be diagnosed with invasive breast cancer over their lifetimes, according to the American Cancer Society—and for the year 2024, it was estimated that more than 300,000 women in the United States would be diagnosed with breast cancer, and more than 40,000 would die from the disease. If we want to reduce these numbers, increasing our understanding of how breast cancer operates in order to improve prevention, detection, and treatment methods is paramount.
The lab of Assistant Professor Liang Liu, PhD, at The Hormel Institute, University of Minnesota, has published a paper appearing in the scientific journal Cell Death & Disease that examines how a protein called TXNIP might help fight breast cancer by slowing its growth and spread throughout the body.
The scientists focused on two different types of breast cancer cells:
- MDA-MB-231: Associated with triple-negative breast cancer and naturally high TXNIP levels
- HCC-1954: Associated with HER2-positive breast cancer, low TXNIP levels
They also investigated how TXNIP interacts with other proteins—especially calpastatin (CAST) and interleukin-24 (IL-24)—and how these interactions influence a cancer-promoting cellular signal called STAT3.
The researchers found:
- Reducing TXNIP in MDA-MB-231 cells led to faster tumor growth and spread.
- Increasing TXNIP in HCC-1954 cells slowed cell growth and movement, raised harmful reactive oxygen levels (ROS), and disrupted energy use, showing its anti-cancer effects.
- Tests revealed calpastatin (CAST) as a new partner of TXNIP in both cell types; unexpectedly, CAST was found to boost tumor growth, opposing TXNIP’s effects.
- Higher TXNIP levels were linked to more IL-24 (which kills cancer cells) and less active STAT3 (which drives cancer).
- Cells with more TXNIP responded better to IL-24 and a STAT3-blocking drug (WP1066), suggesting TXNIP could predict treatment success.
The study yielded some surprising findings that warrant further scientific exploration.
“It’s surprising that calpastatin (CAST), a protein TXNIP binds to, actually promotes tumor growth in both cell types tested. CAST was known for a different role (stopping cell damage), so its cancer-helping behavior here is unexpected and worth exploring further,” Dr. Liu said. “In HCC-1954 cells, extra TXNIP first shrank tumors, but after four weeks, growth sped up. This shift hints that cancer might adapt or resist over time, possibly due to CAST, making TXNIP’s effects a puzzle to solve.”
“These observations illustrate the complexity of cancer’s adaptive responses and serve as a reminder that cancer is sneaky and tough to beat,” Dr. Liu said. “The findings could lead to trials for TXNIP-based therapies, tools to better forecast treatment success, and a clearer picture of breast cancer’s inner workings.”
This study is significant for its contributions to understanding TXNIP’s role in breast cancer and its therapeutic potential:
- High TXNIP levels might signal which patients will benefit from specific therapies, helping doctors tailor their treatments more effectively.
- TXNIP’s ability to fight cancer by increasing oxygen stress, boosting cancer-killing IL-24, and blocking the cancer-promoting STAT3 signal makes it a promising target for future drugs. Pairing it with treatments like WP1066, a STAT3 inhibitor, could improve breast cancer care.
- Uncovering how TXNIP works in combination with CAST, IL-24, and STAT3 sheds new light on what fuels aggressive breast cancers, like triple-negative and HER2-positive types.
The study’s authors are continuing research in this area to bring these findings closer to real-world use to transform outcomes for breast cancer patients.
Beyond cancer, better understanding of TXNIP has applications across multiple health fields. For example, TXNIP helps regulate blood sugar and cell stress, making it significant in diabetes research.
The Hormel Institute’s Post-Doctoral Associate Jasvinder Singh, PhD; Post-Doctoral Associate Bindeshwar Sah; and Executive Director Robert Clarke, PhD, at The Hormel Institute are also listed as authors of the paper.
You can read the paper here: https://pmc.ncbi.nlm.nih.gov/articles/PMC11965567/
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Founded in 1942 by The Hormel Foundation, The Hormel Institute, University of Minnesota, makes scientific advancements that enhance wellbeing and extend human life. For more than 80 years, we have pursued our mission to conduct research and provide education in the biological sciences with applications in medicine and agriculture. A part of the University of Minnesota's Research and Innovation Office, The Hormel Institute partners with the region's leading biomedical research facilities, including Mayo Clinic.