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Tumor cell-adipocyte gap junctions activate lipolysis and contribute to breast tumorigenesis

Author

Listed:
  • Jeremy Williams

    (University of California, San Francisco
    University of California, San Francisco)

  • Roman Camarda

    (University of California, San Francisco
    University of California, San Francisco)

  • Serghei Malkov

    (University of California, San Francisco)

  • Lisa J. Zimmerman

    (Vanderbilt University School of Medicine
    Vanderbilt-Ingram Cancer Center)

  • Suzanne Manning

    (Vanderbilt University School of Medicine)

  • Dvir Aran

    (Israel Institute of Technology
    Israel Institute of Technology)

  • Andrew Beardsley

    (University of California, San Francisco
    University of California, San Francisco)

  • Daniel Mark

    (University of California, San Francisco)

  • Rachel Nakagawa

    (University of California, San Francisco
    University of California, San Francisco)

  • Yong Chen

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    Huazhong University of Science and Technology)

  • Charles Berdan

    (University of California, Berkeley
    University of California, Berkeley
    University of California, Berkeley)

  • Sharon M. Louie

    (University of California, Berkeley
    University of California, Berkeley
    University of California, Berkeley)

  • Celine Mahieu

    (University of California, San Francisco)

  • Daphne Superville

    (University of California, San Francisco
    University of California, San Francisco)

  • Juliane Winkler

    (University of California, San Francisco
    University of California, San Francisco
    Medical University of Vienna)

  • Elizabeth Willey

    (University of California, San Francisco
    University of California, San Francisco)

  • Erica J. Hutchins

    (University of California, San Francisco
    University of California, San Francisco)

  • John D. Gagnon

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

  • Seda Kilinc Avsaroglu

    (University of California, San Francisco)

  • Kosaku Shinoda

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    Albert Einstein College of Medicine)

  • Matthew Gruner

    (University of California, San Francisco)

  • Hiroshi Nishida

    (Harvard Medical School
    Howard Hughes Medical Institute)

  • K. Mark Ansel

    (University of California, San Francisco
    University of California, San Francisco)

  • Zena Werb

    (University of California, San Francisco
    University of California, San Francisco)

  • Daniel K. Nomura

    (University of California, Berkeley
    University of California, Berkeley
    University of California, Berkeley)

  • Shingo Kajimura

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco
    Harvard Medical School)

  • Atul J. Butte

    (Israel Institute of Technology)

  • Melinda E. Sanders

    (Vanderbilt University School of Medicine)

  • Daniel C. Liebler

    (Vanderbilt University School of Medicine
    Vanderbilt-Ingram Cancer Center)

  • Hope S. Rugo

    (University of California, San Francisco
    City of Hope Comprehensive Cancer Center)

  • Gregor Krings

    (University of California, San Francisco)

  • John A. Shepherd

    (University of Hawaii)

  • Andrei Goga

    (University of California, San Francisco
    University of California, San Francisco
    University of California, San Francisco)

Abstract

A pro-tumorigenic role for adipocytes has been identified in breast cancer, and reliance on fatty acid catabolism found in aggressive tumors. The molecular mechanisms by which tumor cells coopt neighboring adipocytes, however, remain incompletely understood. Here, we describe a direct interaction linking tumorigenesis to adjacent adipocytes. We examine breast tumors and their normal adjacent tissue from several patient cohorts, patient-derived xenografts, and mouse models, and find that lipolysis and lipolytic signaling are activated in neighboring adipose tissue. We find that functional gap junctions form between breast cancer cells and adipocytes. As a result, cAMP is transferred from breast cancer cells to adipocytes and activates lipolysis in a gap junction-dependent manner. We find that connexin 31 (GJB3) promotes receptor triple negative breast cancer growth and activation of lipolysis in vivo. Thus, direct tumor cell-adipocyte interaction contributes to tumorigenesis and may serve as a new therapeutic target in breast cancer.

Suggested Citation

  • Jeremy Williams & Roman Camarda & Serghei Malkov & Lisa J. Zimmerman & Suzanne Manning & Dvir Aran & Andrew Beardsley & Daniel Mark & Rachel Nakagawa & Yong Chen & Charles Berdan & Sharon M. Louie & C, 2025. "Tumor cell-adipocyte gap junctions activate lipolysis and contribute to breast tumorigenesis," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62486-3
    DOI: 10.1038/s41467-025-62486-3
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