SOX2 control activation of dormant prostate cancer cells in bone metastases by promoting CCNE2 gene expression

SOX2 通过促进 CCNE2 基因表达控制骨转移中休眠前列腺癌细胞的激活

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作者:Min Deng, Pei-Zheng Huang, Ze-Yu Huang, Ting-Ting Chen, Xing Luo, Chao-Yu Liao, Wen-Hao Xu, Jiang Zhao, Qing-Jian Wu, Ji Zheng

Background

Cancer stem cells (CSCs) have a powerful tumor initiation ability, which can promote the early dissemination of single disseminated tumor cells (DTCs), leading to tumor progression. SOX2, a pluripotent inducible transcription factor, is key to maintaining self-renewal and pluripotency of prostate cancer stem cells. However, there is a lack of comprehensive understanding of how SOX2 regulates DTCs dormancy and proliferation in the bone marrow microenvironment.

Conclusion

The expression of SOX2 affects multiple phenotypes related to dormancy, proliferation and invasion of prostate cancer, and may indirectly activate the dormant prostate cancer cells through the downstream target gene CCNE2, thus affecting the progression and bone metastasis of prostate cancer.

Results

By constructing a mouse bone metastasis model to simulate the progression of prostate cancer with bone metastasis, the bone tissue immunofluorescence showed that SOX2 expression increased with the progression of prostate cancer in the bone marrow microenvironment. We validated this phenomenon with publicly available single-cell and transcriptome datasets and found that SOX2 is involved in multiple phenotypes associated with prostate cancer dormancy, proliferation, and invasion. Further, CCNE2, a potential target downstream of SOX2, was identified through multiple transcription factor databases and protein interaction networks.

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