On December 27, 2024, Professor Wang Xinghuan and his team from Zhongnan Hospital of Wuhan University published the title "Concurrent DNA hypomethylation and epigenomic reprogramming driven by androgen receptor binding in bladder cancer oncogenesis"[1] in the internationally renowned academic journal Clinical and Translational Medicine (Top of the first region of the Chinese Academy of Sciences).
In the vast ocean of tumor research, our research group continues to explore the deep mechanism of tumor occurrence and development. Tumor heterogeneity in bladder cancer leads to resistance to treatment and immune escape, which affects clinical prognosis. However, the molecular mechanisms and cell evolution trajectories that promote intracellular heterogeneity in bladder cancer remain unclear.
In the early stage, we carried out single-cell timing analysis on bladder cancer tissues with different stages using EpiTrace, a tracing technology that can trace cell age and evolution, identified a TM4SF1 positive subpopulation of cancer cells (TPCS), which is a key node in epigenetic evolution of bladder cancer and can cause tumor heterogeneity and thus drive tumor development.
There is a gender bias in the incidence of bladder cancer, which is significantly higher in men than in women, but women tend to be diagnosed at a more advanced stage and have a worse prognosis. Our research group used CUT&Tag sequencing technology to accurately map the role of androgen receptor (AR) in bladder cancer patients, and found that AR can promote the heterogeneous development of tumor cells by changing DNA methylation patterns and regulating gene expression. In addition, this study reveals the role of FOXA1, a key transcription factor, in bladder cancer development, particularly how it drives tumor growth and evolution through its interaction with AR in men.
By analyzing different types of bladder cancer cell lines, the research group further confirmed the role of AR and FOXA1 in regulating gene expression and epigenetic state in cancer cells, and found that in bladder cancer cells, the combination of AR can lead to DNA demethylation and epigenetic mark changes, thus promoting the evolution of bladder cancer cells. And promote the generation of intra-tumor heterogeneity.
In summary, CUT&Tag sequencing technology was used in this study to accurately map the "action trajectory" of AR in the evolution of bladder cancer, and to reveal the driving mechanism of heterogeneous evolution of bladder cancer and the causes of gender bias from the perspective of AR.
References:
[1] Xiao Y, Ju L, Jin W, et al. Concurrent DNA hypomethylation and epigenomic reprogramming driven by androgen receptor binding in bladder cancer oncogenesis. Clin Transl Med, 2025, 15: e70153.
Links:
https://doi.org/10.1002/ctm2.70153