IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v12y2021i1d10.1038_s41467-021-21976-w.html
   My bibliography  Save this article

Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer

Author

Listed:
  • Baotong Zhang

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Yixiang Li

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Qiao Wu

    (Nankai University College of Life Sciences)

  • Lin Xie

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University
    Third Affiliated Hospital of Kunming Medical University, Cancer Hospital of Yunnan Province)

  • Benjamin Barwick

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Changying Fu

    (Nankai University College of Life Sciences
    Southern University of Science and Technology School of Medicine)

  • Xin Li

    (Augusta University)

  • Daqing Wu

    (Augusta University)

  • Siyuan Xia

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Jing Chen

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Wei Ping Qian

    (Winship Cancer Institute, Emory University
    Emory University School of Medicine)

  • Lily Yang

    (Winship Cancer Institute, Emory University
    Emory University School of Medicine)

  • Adeboye O. Osunkoya

    (Winship Cancer Institute, Emory University
    Emory University School of Medicine)

  • Lawrence Boise

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Paula M. Vertino

    (Winship Cancer Institute, Emory University
    Emory University School of Medicine)

  • Yichao Zhao

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Menglin Li

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Hsiao-Rong Chen

    (Emory University)

  • Jeanne Kowalski

    (Emory University)

  • Omer Kucuk

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Wei Zhou

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University)

  • Jin-Tang Dong

    (Emory University School of Medicine
    Winship Cancer Institute, Emory University
    Southern University of Science and Technology School of Medicine)

Abstract

Advanced prostate cancer (PCa) often develops bone metastasis, for which therapies are very limited and the underlying mechanisms are poorly understood. We report that bone-borne TGF-β induces the acetylation of transcription factor KLF5 in PCa bone metastases, and acetylated KLF5 (Ac-KLF5) causes osteoclastogenesis and bone metastatic lesions by activating CXCR4, which leads to IL-11 secretion, and stimulating SHH/IL-6 paracrine signaling. While essential for maintaining the mesenchymal phenotype and tumorigenicity, Ac-KLF5 also causes resistance to docetaxel in tumors and bone metastases, which is overcome by targeting CXCR4 with FDA-approved plerixafor. Establishing a mechanism for bone metastasis and chemoresistance in PCa, these findings provide a rationale for treating chemoresistant bone metastasis of PCa with inhibitors of Ac-KLF5/CXCR4 signaling.

Suggested Citation

  • Baotong Zhang & Yixiang Li & Qiao Wu & Lin Xie & Benjamin Barwick & Changying Fu & Xin Li & Daqing Wu & Siyuan Xia & Jing Chen & Wei Ping Qian & Lily Yang & Adeboye O. Osunkoya & Lawrence Boise & Paul, 2021. "Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer," Nature Communications, Nature, vol. 12(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21976-w
    DOI: 10.1038/s41467-021-21976-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-021-21976-w
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-021-21976-w?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Meixia Che & Aashi Chaturvedi & Sarah A. Munro & Samuel P. Pitzen & Alex Ling & Weijie Zhang & Josh Mentzer & Sheng-Yu Ku & Loredana Puca & Yanyun Zhu & Andries M. Bergman & Tesa M. Severson & Colleen, 2021. "Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Pamela X. Y. Soh & Naledi Mmekwa & Desiree C. Petersen & Kazzem Gheybi & Smit van Zyl & Jue Jiang & Sean M. Patrick & Raymond Campbell & Weerachai Jaratlerdseri & Shingai B. A. Mutambirwa & M. S. Rian, 2023. "Prostate cancer genetic risk and associated aggressive disease in men of African ancestry," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21976-w. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.