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How Does STAG2 Promote Invasion of Muscle-Invasive Bladder Cancer?

By: Victoria Kuhr, BA
Posted: Friday, May 6, 2022

Sarah R. Athans, PhD, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, and colleagues propose that stromal antigen 2 (STAG2) functions as a transcriptional repressor and promotes movement and invasion of muscle-invasive bladder cancer. In fact, the loss of STAG2 protein appears to lead to better outcomes in patients with muscle-invasive bladder cancer. Additionally, the study authors indicate STAG2 protein expression may function as a potential prognostic biomarker. These study findings were presented at the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 786/14).

“Our current work is utilizing a large drug screen of FDA-approved agents to identify vulnerabilities of tumor cells lacking stromal antigen 2 to benefit a large proportion of patients with stromal antigen 2–mutant tumors,” said the authors.

The study analyzed knocked-down STAG2 in T24 muscle-invasive bladder cancer cells using two hairpin RNAs. Scrambled hairpin RNAs served as the control in all experiments. RNA sequencing and chromatin immunoprecipitation sequencing were performed on knockdown and control T24 cell lines.

The study discovered that genes with increased expression after STAG2 knockdown were enriched for STAG2-binding sites, yet genes with decreased expression did not show significant enrichment. This finding suggests that STAG2 functions as a transcriptional repressor, so the authors focused on genes with increased expression after STAG2 knockdown. A time-lapse microscopy and invasion assays were performed to quantitatively determine cell movement over time on in vitro muscle-invasive bladder cancer cells. When the in vitro muscle-invasive bladder cancer cells were compared with controls, T24 cells with STAG2 knockdown had significantly reduced displacement, speed, and invasion of cancer cells.

Disclosure: The study authors reported no conflicts of interest.


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