Phosphorylation of androgen receptor by mTORC1 promotes liver steatosis and tumorigenesis
| Autor: | Qian-Nan Ren, Hui-Zhong Zhang, Xiaoxing Li, X. F.Steven Zheng, Chao-Yue Sun, Xue-Feng Yang, Yu-Feng Zhou, Mei-Yin Zhang, Hong Zhang, Hai-Qiang Mai, Shi-Juan Mai, Jian-Wu Long, Minshan Chen, Hui-Yun Wang |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Carcinoma Hepatocellular medicine.drug_class Carcinogenesis mTORC1 Mechanistic Target of Rapamycin Complex 1 medicine.disease_cause Prostate cancer Mice medicine Animals Humans Phosphorylation neoplasms PI3K/AKT/mTOR pathway Hepatology business.industry Liver Neoplasms Androgen medicine.disease digestive system diseases Androgen receptor Fatty Liver Cell Transformation Neoplastic Receptors Androgen Hepatocellular carcinoma Cancer research Androgens business |
| Zdroj: | Hepatology (Baltimore, Md.). 75(5) |
| ISSN: | 1527-3350 |
| Popis: | Androgen receptor (AR) has been reported to play an important role in the development and progression of man's prostate cancer. Hepatocellular carcinoma (HCC) is also male-dominant, but the role of AR in HCC remains poorly understood. Mechanistic target of rapamycin complex 1 (mTORC1) also has been reported to be highly activated in HCC. In this study, we aimed to explore the role of AR phosphorylation and its relationship with mTORC1 in hepatocarcinogenesis.In vitro experiment, we observed that mTORC1 interacts with hepatic AR and phosphorylates it at S96 in response to nutrient and mitogenic stimuli in HCC cells. S96 phosphorylation promotes the stability, nuclear localization, and transcriptional activity of AR, which enhances de novo lipogenesis and proliferation in hepatocytes and induces liver steatosis and hepatocarcinogenesis in mice independently and cooperatively with androgen. Furthermore, high ARAR S96 phosphorylation by mTORC1 drives liver steatosis and HCC development and progression independently and cooperatively with androgen, which not only explains why HCC is man-biased but also provides a target molecule for prevention and treatment of HCC and a potential survival predictor in patients with HCC. |
| Databáze: | OpenAIRE |
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