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

Author

Listed:
  • Qingbo Huang

    (Chinese PLA General Hospital
    University of Rochester Medical Center)

  • Yin Sun

    (University of Rochester Medical Center)

  • Xin Ma

    (Chinese PLA General Hospital)

  • Yu Gao

    (Chinese PLA General Hospital)

  • Xintao Li

    (Chinese PLA General Hospital)

  • Yuanjie Niu

    (Tianjin Medical University)

  • Xu Zhang

    (Chinese PLA General Hospital)

  • Chawnshang Chang

    (University of Rochester Medical Center
    Tianjin Medical University
    China Medical University/Hospital)

Abstract

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 HIF2α/VEGF-A expression via binding to the promoter region of HIF2α. 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.

Suggested Citation

  • Qingbo Huang & Yin Sun & Xin Ma & Yu Gao & Xintao Li & Yuanjie Niu & Xu Zhang & Chawnshang Chang, 2017. "Androgen receptor increases hematogenous metastasis yet decreases lymphatic metastasis of renal cell carcinoma," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-00701-6
    DOI: 10.1038/s41467-017-00701-6
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