Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.
Novel Oncogenic Transcription Factor Cooperation in RB-Deficient Cancer.
复制标题
RB缺陷型癌症中新的致癌转录因子合作。
DOI：
10.1158/0008-5472.can-21-1159
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发表时间：
2022-01-15
期刊：
影响因子：
11.2
通讯作者：
中科院分区：
文献类型：
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作者：
本研究发现前列腺癌的RB缺失驱动AR和E2F1作为转录的共调节因子，这与晚期疾病的进展有关。视网膜母细胞瘤肿瘤抑制因子（RB）是e2f依赖性转录的关键调节因子，控制多种蛋白发生网络，包括但不限于细胞周期控制。在此，对前列腺癌等基因模型中RB缺失后E2F1功能的全基因组评估揭示了意想不到的重新定位和与致癌转录因子的合作，包括疾病进展的主要驱动因素雄激素受体（AR）。进一步的研究表明，观察到的AR/E2F1合作引发了新的转录网络，促进癌症表型，特别是与逃避细胞死亡有关的表型。这些观察结果反映在人类疾病的评估中，表明AR/E2F1协同组在前列腺癌中的临床相关性。总之，这些研究揭示了RB缺失诱导癌症进展的新机制，并强调了了解E2F1功能靶点的重要性。本研究发现前列腺癌的RB缺失驱动AR和E2F1作为转录的共调节因子，这与晚期疾病的进展有关。
This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease. The retinoblastoma tumor suppressor (RB) is a critical regulator of E2F-dependent transcription, controlling a multitude of protumorigenic networks including but not limited to cell-cycle control. Here, genome-wide assessment of E2F1 function after RB loss in isogenic models of prostate cancer revealed unexpected repositioning and cooperation with oncogenic transcription factors, including the major driver of disease progression, the androgen receptor (AR). Further investigation revealed that observed AR/E2F1 cooperation elicited novel transcriptional networks that promote cancer phenotypes, especially as related to evasion of cell death. These observations were reflected in assessment of human disease, indicating the clinical relevance of the AR/E2F1 cooperome in prostate cancer. Together, these studies reveal new mechanisms by which RB loss induces cancer progression and highlight the importance of understanding the targets of E2F1 function. This study identifies that RB loss in prostate cancer drives cooperation between AR and E2F1 as coregulators of transcription, which is linked to the progression of advanced disease.