A team of researchers from the University of Hawaii Cancer Center published a study on October 26 sharing new findings on how the protein known as HMGB1 helps mesothelioma cells grow and proliferate, potentially shedding more light on the exact mechanisms driving the deadly cancer.
The researchers found that HMGB1 interacts with the BAP1 gene, an important tumor-suppressing gene that has been highly linked with mesothelioma. Although the mechanisms that drove BAP1 expression were previously unknown, the researchers found that the HMGB1 protein drove overexpression of BAP1, thus promoting the proliferation of mesothelioma cancer cells.
“Our discovery that HMGB1-driven BAP1 overexpression supports cancer growth provides a mechanistic rationale for the improved survival observed in mesothelioma patients with somatic BAP1 inactivating mutations,” according to the abstract.
What the Study Means for Mesothelioma
Research into the BAP1 gene has shown that it plays an important role in mesothelioma, a deadly cancer caused by exposure to the mineral asbestos. BAP1 helps control cell growth, cell division, and cell death, and helps prevent cells from becoming cancerous.
Loss or mutation of BAP1 has been shown to increase the risk of cancer, as cells have less ability to repair damaged DNA. Studies have shown that a high proportion of mesothelioma patients tend to have BAP1 deficiencies.
However, exactly what drives BAP1 expression was previously a mystery, one that the Hawaii study has shed some light on. The study found that the HMGB1 protein binds to BAP1 promoters and activates its transcription, leading to an overexpression of BAP1.
Rather than suppress cancer cell growth, this actually promotes the proliferation, growth, and migration of mesothelioma cells. In the meantime, loss of the HMGB1 protein in turn causes a significant loss of BAP1 levels.
The discovery of this relationship between the HMGB1 protein and the BAP1 gene is a new development, and one that could prove key into fully understanding how mesothelioma works at the cellular level.
Further Research into Mesothelioma Proteins
The study identified the relationship between the HMGB1 protein and the BAP1 gene as a potential subject for further clinical studies for the treatment of mesothelioma.
The findings also highlight the complex role of BAP1 in mesothelioma. While mutations that inactivate BAP1 can contribute to cancer development, the researchers found that mesothelioma cells lacking BAP1 were less aggressive in experimental models. With further research, targeting the HMGB1-BAP1 interaction to reduce BAP1 expression may offer possible new treatment strategies for mesothelioma.
The researchers wrote that their data regarding what they call the “HMGB1-BAP1 axis” have been validated by results from an ongoing trial being performed at the U.S. National Cancer Institute Bethesda Medical Center.
As research continues to proceed into how mesothelioma grows and spreads at the cellular level, they provide the possibility that new avenues of study could reveal themselves, and provide new targets for novel treatments.
Sources & Author
- HMGB1 directly activates BAP1 transcription to sustain tumor growth in mesothelioma. Cell Death & Differentiation. Retrieved from https://www.nature.com/articles/s41418-026-01892-6. Accessed on 10/26/2026.
