Knockout of Akt1/2 suppresses the metastasis of human prostate cancer cells CWR22rv1 in vitro and in vivo
| Autor: | Xiaofan Chen, Bing Su, Lijuan Zhang, Wenfang Zhuang, Wei Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Gene Expression AKT1 AKT2 Metastasis Androgen deprivation therapy Mice 03 medical and health sciences Prostate cancer 0302 clinical medicine In vivo Cell Line Tumor Animals Humans metastasis Medicine Neoplasm Metastasis Protein kinase B Cells Cultured business.industry Akt Prostatic Neoplasms Original Articles Cell Biology prostate cancer medicine.disease Immunohistochemistry Gene Expression Regulation Neoplastic Disease Models Animal Protein Transport 030104 developmental biology Receptors Androgen Gene Knockdown Techniques 030220 oncology & carcinogenesis Gene Targeting Cancer cell Cancer research Heterografts Molecular Medicine Original Article FOXO business Proto-Oncogene Proteins c-akt Protein Binding AR |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/jcmm.16246 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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