Androgen receptor increases hematogenous metastasis yet decreases lymphatic metastasis of renal cell carcinoma

作者：Huang, Qingbo; Sun, Yin; Ma, Xin; Gao, Yu; Li, Xintao; Niu, Yuanjie; Zhang, Xu^*; Chang, Chawnshang^*

来源：Nature Communications, 2017, 8(1): 918.

DOI：10.1038/s41467-017-00701-6

• ENDOTHELIAL GROWTH-FACTOR
• PROMOTES TUMOR-METASTASIS
• VEGF-C
• EXPRESSION
• CANCER
• LYMPHANGIOGENESIS
• IDENTIFICATION
• COMPLEMENTARY
• PROGNOSIS
• THERAPY

Clear cell renal cell carcinoma (ccRCC) is a gender-biased tumor. Here we report that there is also a gender difference between pulmonary metastasis and lymph node metastasis showing that the androgen receptor (AR)-positive ccRCC may prefer to metastasize to lung rather than to lymph nodes. A higher AR expression increases ccRCC hematogenous metastasis yet decreases ccRCC lymphatic metastases. Mechanism dissection indicates that AR enhances miR-185-5p expression via binding to the androgen response elements located on the promoter of miR-185-5p, which suppresses VEGF-C expression via binding to its 3' UTR. In contrast, AR-enhanced miR-185-5p also promotes HIF2 alpha/VEGF-A expression via binding to the promoter region of HIF2 alpha. Together, these results provide a unique mechanism by which AR can either increase or decrease ccRCC metastasis at different sites and may help us to develop combined therapies using anti-AR and anti-VEGF-C compounds to better suppress ccRCC progression.

• 出版日期2017-10-13
• 单位中国医科大学; 天津医科大学; 中国人民解放军总医院