IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30484-4.html
   My bibliography  Save this article

PRRX1 is a master transcription factor of stromal fibroblasts for myofibroblastic lineage progression

Author

Listed:
  • Keun-Woo Lee

    (Sungkyunkwan University)

  • So-Young Yeo

    (Sungkyunkwan University)

  • Jeong-Ryeol Gong

    (Korea Advanced Institute of Science and Technology)

  • Ok-Jae Koo

    (Geumcheon)

  • Insuk Sohn

    (Gangnam-daero)

  • Woo Yong Lee

    (Sungkyunkwan University School of Medicine)

  • Hee Cheol Kim

    (Sungkyunkwan University School of Medicine)

  • Seong Hyeon Yun

    (Sungkyunkwan University School of Medicine)

  • Yong Beom Cho

    (Sungkyunkwan University School of Medicine)

  • Mi-Ae Choi

    (Sungkyunkwan University)

  • Sugyun An

    (Korea Advanced Institute of Science and Technology)

  • Juhee Kim

    (Korea Advanced Institute of Science and Technology)

  • Chang Ohk Sung

    (University of Ulsan College of Medicine)

  • Kwang-Hyun Cho

    (Korea Advanced Institute of Science and Technology)

  • Seok-Hyung Kim

    (Sungkyunkwan University
    Sungkyunkwan University School of Medicine
    Sungkyunkwan University School of Medicine)

Abstract

Although stromal fibroblasts play a critical role in cancer progression, their identities remain unclear as they exhibit high heterogeneity and plasticity. Here, a master transcription factor (mTF) constructing core-regulatory circuitry, PRRX1, which determines the fibroblast lineage with a myofibroblastic phenotype, is identified for the fibroblast subgroup. PRRX1 orchestrates the functional drift of fibroblasts into myofibroblastic phenotype via TGF-β signaling by remodeling a super-enhancer landscape. Such reprogrammed fibroblasts have myofibroblastic functions resulting in markedly enhanced tumorigenicity and aggressiveness of cancer. PRRX1 expression in cancer-associated fibroblast (CAF) has an unfavorable prognosis in multiple cancer types. Fibroblast-specific PRRX1 depletion induces long-term and sustained complete remission of chemotherapy-resistant cancer in genetically engineered mice models. This study reveals CAF subpopulations based on super-enhancer profiles including PRRX1. Therefore, mTFs, including PRRX1, provide another opportunity for establishing a hierarchical classification system of fibroblasts and cancer treatment by targeting fibroblasts.

Suggested Citation

  • Keun-Woo Lee & So-Young Yeo & Jeong-Ryeol Gong & Ok-Jae Koo & Insuk Sohn & Woo Yong Lee & Hee Cheol Kim & Seong Hyeon Yun & Yong Beom Cho & Mi-Ae Choi & Sugyun An & Juhee Kim & Chang Ohk Sung & Kwang-, 2022. "PRRX1 is a master transcription factor of stromal fibroblasts for myofibroblastic lineage progression," Nature Communications, Nature, vol. 13(1), pages 1-23, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30484-4
    DOI: 10.1038/s41467-022-30484-4
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30484-4
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30484-4?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
    ---><---

    References listed on IDEAS

    as
    1. Tiago A. Schieber & Laura Carpi & Albert Díaz-Guilera & Panos M. Pardalos & Cristina Masoller & Martín G. Ravetti, 2017. "Quantification of network structural dissimilarities," Nature Communications, Nature, vol. 8(1), pages 1-10, April.
    2. Charles Y. Lin & Serap Erkek & Yiai Tong & Linlin Yin & Alexander J. Federation & Marc Zapatka & Parthiv Haldipur & Daisuke Kawauchi & Thomas Risch & Hans-Jörg Warnatz & Barbara C. Worst & Bensheng Ju, 2016. "Active medulloblastoma enhancers reveal subgroup-specific cellular origins," Nature, Nature, vol. 530(7588), pages 57-62, February.
    3. So-Young Yeo & Keun-Woo Lee & Dongkwan Shin & Sugyun An & Kwang-Hyun Cho & Seok-Hyung Kim, 2018. "A positive feedback loop bi-stably activates fibroblasts," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    4. Sung-Young Shin & Taeyong Kim & Ho-Sung Lee & Jun Hyuk Kang & Ji Young Lee & Kwang-Hyun Cho & Do Han Kim, 2014. "The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    5. Rik Derynck & Ying E. Zhang, 2003. "Smad-dependent and Smad-independent pathways in TGF-β family signalling," Nature, Nature, vol. 425(6958), pages 577-584, October.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Keyong Sun & Runda Xu & Fuhai Ma & Naixue Yang & Yang Li & Xiaofeng Sun & Peng Jin & Wenzhe Kang & Lemei Jia & Jianping Xiong & Haitao Hu & Yantao Tian & Xun Lan, 2022. "scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Deblina Banerjee & Sukriti Bagchi & Zhihui Liu & Hsien-Chao Chou & Man Xu & Ming Sun & Sara Aloisi & Zalman Vaksman & Sharon J. Diskin & Mark Zimmerman & Javed Khan & Berkley Gryder & Carol J. Thiele, 2024. "Lineage specific transcription factor waves reprogram neuroblastoma from self-renewal to differentiation," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Erick Armingol & Hratch M. Baghdassarian & Cameron Martino & Araceli Perez-Lopez & Caitlin Aamodt & Rob Knight & Nathan E. Lewis, 2022. "Context-aware deconvolution of cell–cell communication with Tensor-cell2cell," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    4. Chen, Gaolin & Zhou, Shuming & Li, Min & Zhang, Hong, 2022. "Evaluation of community vulnerability based on communicability and structural dissimilarity," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 606(C).
    5. Gao, Cuixia & Tao, Simin & Su, Bin & Mensah, Isaac Adjei & Sun, Mei, 2023. "Exploring renewable energy trade coopetition relationships: Evidence from belt and road countries, 1996-2018," Renewable Energy, Elsevier, vol. 202(C), pages 196-209.
    6. Gerard Llimos & Vincent Gardeux & Ute Koch & Judith F. Kribelbauer & Antonina Hafner & Daniel Alpern & Joern Pezoldt & Maria Litovchenko & Julie Russeil & Riccardo Dainese & Riccardo Moia & Abdurraouf, 2022. "A leukemia-protective germline variant mediates chromatin module formation via transcription factor nucleation," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    7. Yijia Xiang & Yonghui Wu & Shiyong Ye & Junchong Chen & Changhong Cai & Ning Zhu & Xuyong Zhao & Chunlai Zeng, 2019. "Sildenafil May Have an Inhibition Effect on The TGFβ1- Smad2/3 Pathway in PAH Rats," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 15(2), pages 1-6, February.
    8. Alexis Osseni & Aymeric Ravel-Chapuis & Edwige Belotti & Isabella Scionti & Yann-Gaël Gangloff & Vincent Moncollin & Laetitia Mazelin & Remi Mounier & Pascal Leblanc & Bernard J. Jasmin & Laurent Scha, 2022. "Pharmacological inhibition of HDAC6 improves muscle phenotypes in dystrophin-deficient mice by downregulating TGF-β via Smad3 acetylation," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    9. Nie, Chun-Xiao, 2022. "Generalized correlation dimension and heterogeneity of network spaces," Chaos, Solitons & Fractals, Elsevier, vol. 162(C).
    10. Nicholas Sim & Jean-Michel Carter & Kamalakshi Deka & Benita Kiat Tee Tan & Yirong Sim & Suet-Mien Tan & Yinghui Li, 2024. "TWEAK/Fn14 signalling driven super-enhancer reprogramming promotes pro-metastatic metabolic rewiring in triple-negative breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    11. Sébastien Thériault & Zhonglin Li & Erik Abner & Jian’an Luan & Hasanga D. Manikpurage & Ursula Houessou & Pardis Zamani & Mewen Briend & Dominique K. Boudreau & Nathalie Gaudreault & Lily Frenette & , 2024. "Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    12. Saeed, Mahdisoltani & Ramin, Golestanian, 2023. "Nonequilibrium phenomena in driven and active Coulomb field theories," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 631(C).
    13. Tofighy, Sajjad & Charkari, Nasrollah Moghadam & Ghaderi, Foad, 2022. "Link prediction in multiplex networks using intralayer probabilistic distance and interlayer co-evolving factors," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 606(C).
    14. Wang, Xiaoyan & Tang, Ming & Guan, Shuguang & Zou, Yong, 2023. "Quantifying time series complexity by multi-scale transition network approaches," Physica A: Statistical Mechanics and its Applications, Elsevier, vol. 622(C).
    15. Qianxia Li & Huanlei Wu & Bei Chen & Guangyuan Hu & Liu Huang & Kai Qin & Yu Chen & Xianglin Yuan & Zhongxing Liao, 2012. "SNPs in the TGF-β Signaling Pathway Are Associated with Increased Risk of Brain Metastasis in Patients with Non–Small-Cell Lung Cancer," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-11, December.
    16. Min Kyung Lee & Nasim Azizgolshani & Joshua A. Shapiro & Lananh N. Nguyen & Fred W. Kolling & George J. Zanazzi & Hildreth Robert Frost & Brock C. Christensen, 2024. "Identifying tumor type and cell type-specific gene expression alterations in pediatric central nervous system tumors," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    17. Noha A. M. Shendy & Melissa Bikowitz & Logan H. Sigua & Yang Zhang & Audrey Mercier & Yousef Khashana & Stephanie Nance & Qi Liu & Ian M. Delahunty & Sarah Robinson & Vanshita Goel & Matthew G. Rees &, 2024. "Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    18. Royce W. Zhou & Jia Xu & Tiphaine C. Martin & Alexis L. Zachem & John He & Sait Ozturk & Deniz Demircioglu & Ankita Bansal & Andrew P. Trotta & Bruno Giotti & Berkley Gryder & Yao Shen & Xuewei Wu & S, 2022. "A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-17, 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:13:y:2022:i:1:d:10.1038_s41467-022-30484-4. 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.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with 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.