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Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis

Author

Listed:
  • Xianhui Ruan

    (University of California San Diego)

  • Wei Yan

    (University of California San Diego)

  • Minghui Cao

    (University of California San Diego)

  • Ray Anthony M. Daza

    (University of California San Diego)

  • Miranda Y. Fong

    (University of California San Diego
    City of Hope Beckman Research Institute)

  • Kaifu Yang

    (University of California San Diego)

  • Jun Wu

    (City of Hope Beckman Research Institute)

  • Xuxiang Liu

    (City of Hope Beckman Research Institute)

  • Melanie Palomares

    (Cancer Prevention Movement)

  • Xiwei Wu

    (City of Hope Beckman Research Institute)

  • Arthur Li

    (City of Hope Beckman Research Institute)

  • Yuan Chen

    (University of California San Diego
    University of California San Diego)

  • Rahul Jandial

    (Department of Surgery; City of Hope)

  • Nicholas C. Spitzer

    (University of California San Diego
    University of California San Diego)

  • Robert F. Hevner

    (University of California San Diego)

  • Shizhen Emily Wang

    (University of California San Diego
    University of California San Diego)

Abstract

Breast cancer metastasis to the brain is a clinical challenge rising in prevalence. However, the underlying mechanisms, especially how cancer cells adapt a distant brain niche to facilitate colonization, remain poorly understood. A unique metabolic feature of the brain is the coupling between neurons and astrocytes through glutamate, glutamine, and lactate. Here we show that extracellular vesicles from breast cancer cells with a high potential to develop brain metastases carry high levels of miR-199b-5p, which shows higher levels in the blood of breast cancer patients with brain metastases comparing to those with metastatic cancer in other organs. miR-199b-5p targets solute carrier transporters (SLC1A2/EAAT2 in astrocytes and SLC38A2/SNAT2 and SLC16A7/MCT2 in neurons) to hijack the neuron–astrocyte metabolic coupling, leading to extracellular retention of these metabolites and promoting cancer cell growth. Our findings reveal a mechanism through which cancer cells of a non-brain origin reprogram neural metabolism to fuel brain metastases.

Suggested Citation

  • Xianhui Ruan & Wei Yan & Minghui Cao & Ray Anthony M. Daza & Miranda Y. Fong & Kaifu Yang & Jun Wu & Xuxiang Liu & Melanie Palomares & Xiwei Wu & Arthur Li & Yuan Chen & Rahul Jandial & Nicholas C. Sp, 2024. "Breast cancer cell-secreted miR-199b-5p hijacks neurometabolic coupling to promote brain metastasis," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-48740-0
    DOI: 10.1038/s41467-024-48740-0
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