2015年12月31日讯 /生物谷BIOON/ –近日,来自美国艾默里大学医学院的研究人员在国际学术期刊cancer research上发表了一项最新研究进展,他们发现转录因子SOX4在肿瘤抑制因子PTEN缺失诱导的前列腺癌进展中发挥重要作用,这一发现对于前列腺癌联合治疗方法的开发具有一定意义。
前列腺癌是美国男性中一种最为常见的癌症类型之一,严重威胁男性健康,许多研究对前列腺癌发生发展机制进行了深入探讨,但目前对于前列腺癌发生发展机制的了解仍然不完整。
SOX4是一个在许多类型人类癌症中都存在过表达的重要转录因子,其中包括前列腺癌,这表明SOX4可能参与了前列腺癌的发生,为了对这一假设进行验证,艾默里大学医学院的研究人员进行了一系列研究。
在这项研究中,研究人员通过在肿瘤抑制因子Pten缺失的前列腺癌小鼠模型中敲除SOX4对上述假设进行了探究。研究人员发现在成年小鼠的前列腺上皮中完全敲除SOX4能够强烈抑制Pten缺失诱导的肿瘤进展。随后他们又对其中的机制进行了分析,发现SOX4缺失能够降低AKT和β-catenin的激活,从而减弱肿瘤的侵袭性。
研究人员更进一步发现PTEN缺失会诱导SOX4表达,结果导致PI3K-AKT-mTOR信号途径的激活,从而在SOX4和该信号通路之间形成了一个正反馈回路。
总得来说,这项研究发现SOX4是前列腺癌中PTEN-PI3K-AKT信号途径上的一个重要组成成分,这一发现对于开发治疗原发前列腺癌以及晚期前列腺癌的联合治疗方法具有一定启示。(基因宝jiyinbao.com)
本文系生物谷原创编译整理。欢迎转载!转载请注明来源并附原文链接。更多资讯请下载生物谷资讯APP。
SOX4 is essential for prostate tumorigenesis initiated by PTEN ablation
Birdal Bilir1, Adeboye O Osunkoya2, W. Guy Wiles IV3, Soma Sannigrahi2, Veronique Lefebvre4, Daniel Metzger5, Demetri D Spyropoulos6, W. David Martin3, and Carlos S. Moreno
Understanding remains incomplete of the mechanisms underlying initiation and progression of prostate cancer, the most commonly diagnosed cancer in American men. The transcription factor SOX4 is overexpressed in many human cancers, including prostate cancer, suggesting it may participate in prostate tumorigenesis. In this study, we investigated this possibility by genetically deleting Sox4 in a mouse model of prostate cancer initiated by loss of the tumor suppressor Pten. We found that specific homozygous deletion of Sox4 in the adult prostate epithelium strongly inhibited tumor progression initiated by homozygous loss of Pten. Mechanistically, Sox4 ablation reduced activation of AKT and 尾-catenin, leading to an attenuated invasive phenotype. Furthermore, SOX4 expression was induced by Pten loss as a result of the activation of PI3K-AKT-mTOR signaling, suggesting a positive feedback loop between SOX4 and PI3K-AKT-mTOR activity. Collectively, our findings establish that SOX4 is a critical component of the PTEN-PI3K-AKT pathway in prostate cancer, with potential implications for combination targeted therapies against both primary and advanced prostate cancers.