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STAT3-coordinated migration facilitates the dissemination of diffuse large B-cell lymphomas

Author

Listed:
  • Yi-Ru Pan

    (National Yang-Ming University)

  • Chih-Cheng Chen

    (Chang Gung Memorial Hospital
    Chang Gung University)

  • Yu-Tien Chan

    (National Yang-Ming University)

  • Hsiao-Jung Wang

    (Taipei Veterans General Hospital)

  • Fan-Tso Chien

    (Academia Sinica)

  • Yeng-Long Chen

    (Academia Sinica)

  • Jing-Lan Liu

    (Chang Gung Memorial Hospital)

  • Muh-Hwa Yang

    (National Yang-Ming University
    National Yang-Ming University
    Taipei Veterans General Hospital)

Abstract

The motile characteristics and mechanisms that drive the dissemination of diffuse large B-cell lymphoma (DLBCL) are elusive. Here, we show that DLBCL initiates dissemination through activating STAT3-mediated amoeboid migration. Mechanistically, STAT3 activates RHOH transcription, which competes with the RhoGDP dissociation inhibitor RhoGDIγ to activate RhoA. In addition, activated STAT3 regulates microtubule dynamics and releases ARHGEF2 to activate RhoA. Both the JAK inhibitor ruxolitinib and the microtubule stabilizer Taxol suppress DLBCL cell dissemination in vivo. A clinical DLBCL sample analysis shows that STAT3-driven amoeboid movement is particularly important for the transition from stage I to stage II. This study elucidates the mechanism of DLBCL dissemination and progression and highlights the potential of combating advanced DLBCL with a JAK/STAT inhibitor or microtubule stabilizer to reduce DLBCL motility; these findings may have a great impact on the development of patient-tailored treatments for DLBCL.

Suggested Citation

  • Yi-Ru Pan & Chih-Cheng Chen & Yu-Tien Chan & Hsiao-Jung Wang & Fan-Tso Chien & Yeng-Long Chen & Jing-Lan Liu & Muh-Hwa Yang, 2018. "STAT3-coordinated migration facilitates the dissemination of diffuse large B-cell lymphomas," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06134-z
    DOI: 10.1038/s41467-018-06134-z
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