Medical laboratory, Shidong Hospital Affiliated to University of Shanghai for Science and Technology, Shanghai, China.
Department of Laboratory Medicine, The Third Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
J Cell Mol Med. 2021 Feb;25(3):1546-1553. doi: 10.1111/jcmm.16246. Epub 2020 Dec 29.
Although primary androgen deprivation therapy resulted in tumour regression, unfortunately, majority of prostate cancer progress to a lethal castration-resistant prostate cancer, finally die to metastasis. The mutual feedback between AKT and AR pathways plays a vital role in the progression and metastasis of prostate cancer. Therefore, the treatment of a single factor will eventually inevitably lead to failure. Therefore, better understanding of the molecular mechanisms underlying metastasis is critical to the development of new and more effective therapeutic agents. In this study, we created prostate cancer CWR22rv1 cells with the double knockout of Akt1 and Akt2 genes through CRISPR/Cas9 method to investigate the effect of Akt in metastasis of prostate cancer. It was found that knockout of Akt1/2 resulted in markedly reduced metastasis in vitro and in vivo, and appeared to interfere AR nuclear translocation through regulating downstream regulatory factor, FOXO proteins. It suggests that some downstream regulatory factors in the AKT and AR interaction network play a vital role in prostate cancer metastasis and are potential targeting molecules for prostate cancer metastasis treatment.
尽管初级雄激素剥夺疗法导致肿瘤消退，但不幸的是，大多数前列腺癌进展为致命的去势抵抗性前列腺癌，最终死于转移。AKT 和 AR 通路之间的相互反馈在前列腺癌的进展和转移中起着至关重要的作用。因此，单一因素的治疗最终不可避免地会导致失败。因此，更好地了解转移的分子机制对于开发新的、更有效的治疗药物至关重要。在这项研究中，我们通过 CRISPR/Cas9 方法创建了 Akt1 和 Akt2 基因双敲除的前列腺癌细胞系 CWR22rv1，以研究 Akt 在前列腺癌转移中的作用。结果发现，Akt1/2 的敲除导致体外和体内转移明显减少，并且似乎通过调节下游调节因子 FOXO 蛋白来干扰 AR 核易位。这表明 AKT 和 AR 相互作用网络中的一些下游调节因子在前列腺癌转移中起着至关重要的作用，是前列腺癌转移治疗的潜在靶向分子。
