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Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation

Author

Listed:
  • Bo Jiang

    (Nanjing University)

  • Xiaozhi Zhao

    (Nanjing University)

  • Wei Chen

    (Nanjing University)

  • Wenli Diao

    (Nanjing University)

  • Meng Ding

    (Nanjing University)

  • Haixiang Qin

    (Nanjing University)

  • Binghua Li

    (the Affiliated Hospital of Nanjing University Medical School)

  • Wenmin Cao

    (Nanjing University)

  • Wei Chen

    (Nanjing University)

  • Yao Fu

    (Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School)

  • Kuiqiang He

    (Nanjing University)

  • Jie Gao

    (Nanjing University)

  • Mengxia Chen

    (Nanjing University)

  • Tingsheng Lin

    (Nanjing University)

  • Yongming Deng

    (Nanjing University)

  • Chao Yan

    (Nanjing University)

  • Hongqian Guo

    (Nanjing University)

Abstract

Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific metastasis in renal cancer. LAPTM5 sustains self-renewal and cancer stem cell-like traits of renal cancer cells by blocking the function of lung-derived bone morphogenetic proteins (BMPs). Mechanistic investigations showed that LAPTM5 recruits WWP2, which binds to the BMP receptor BMPR1A and mediates its lysosomal sorting, ubiquitination and ultimate degradation. BMPR1A expression was restored by the lysosomal inhibitor chloroquine. LAPTM5 expression could also serve as an independent predictor of lung metastasis in renal cancer. Lastly, elevation of LAPTM5 expression in lung metastases is a common phenomenon in multiple cancer types. Our results reveal a molecular mechanism underlying lung-specific metastasis and identify LAPTM5 as a potential therapeutic target for cancers with lung metastasis.

Suggested Citation

  • Bo Jiang & Xiaozhi Zhao & Wei Chen & Wenli Diao & Meng Ding & Haixiang Qin & Binghua Li & Wenmin Cao & Wei Chen & Yao Fu & Kuiqiang He & Jie Gao & Mengxia Chen & Tingsheng Lin & Yongming Deng & Chao Y, 2022. "Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31783-6
    DOI: 10.1038/s41467-022-31783-6
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