Northwestern Medicine scientists have uncovered how a testis-specific protein contributes to tumor growth and progression in lung cancer, according to a study published in Science Advances.
Previous research in the laboratory of Lu Wang, PhD, assistant professor of Biochemistry and Molecular Genetics and co-senior author of the study, found that the transcription elongation factor BRDT was overexpressed in lung cancer.
“We looked at the level of BRDT in this lung cancer and we asked the question: ‘If we knock it down, what happens to the lung cancer?’” Wang said.
In the study, Wang and his collaborators developed cell lines derived from patients with small cell lung cancer. When BRDT was suppressed in lung cancer cells, it significantly slowed tumor progression and extended survival in laboratory models.
“We tested the depletion of BRDT by in-vitro studies and also in animals and we’ve demonstrated that this protein is essential for the lung cancer tumor growth in animals,” Wang said.
The study also highlights the complex relationship between BRDT and a related cancer-driving protein, BRD4. While the two share some overlapping functions, BRDT was found to perform certain distinct tasks critical to cancer development. In the study, both proteins were found to play key roles in regulating gene expression, according to Bin Zheng, PhD, an instructor in the Department of Biochemistry and Molecular Genetics and first author of the study.
“Basically, BRDT is a testis-specific version of BRD4 and is mis-expressed in lung cancer and we think that drives cancer,” said Zheng. “In lung cancer cells, BRDT can also release paused RNA polymerase II independently of its bromodomains as we previously demonstrated not to be required for Pol II pause/release function of BRD4”
Building on the findings, Ali Shilatifard, PhD, the Robert Francis Furchgott Professor and chair of Biochemistry and Molecular Genetics and co-senior author of the study, along with Wang and Zheng, will work to develop methods to target BRDT in cancer therapies.
“We have therapeutics moving forward to look at BRD4 and BRDT and that could be a new avenue for lung cancer therapeutics,” Shilatifard said.
Both Shilatifard and Wang are members of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
The study was funded by National Institutes of Health grants R01NS126513, R35GM146979 and R35CA197569.
