IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-36521-0.html
   My bibliography  Save this article

Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma

Author

Listed:
  • Qing Li

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Xiao-Xin Zhang

    (Shanghai Jiao Tong University
    Jiangsu University)

  • Li-Peng Hu

    (Shanghai Jiao Tong University)

  • Bo Ni

    (Shanghai Jiao Tong University)

  • Dong-Xue Li

    (Shanghai Jiao Tong University)

  • Xu Wang

    (Shanghai Jiao Tong University)

  • Shu-Heng Jiang

    (Shanghai Jiao Tong University)

  • Hui Li

    (Shanghai Jiao Tong University)

  • Min-Wei Yang

    (Shanghai Jiao Tong University)

  • Yong-Sheng Jiang

    (Shanghai Jiao Tong University)

  • Chun-Jie Xu

    (Shanghai Jiao Tong University)

  • Xue-Li Zhang

    (Shanghai Jiao Tong University)

  • Yan-Li Zhang

    (Shanghai Jiao Tong University)

  • Pei-Qi Huang

    (Shanghai Jiao Tong University)

  • Qin Yang

    (Shanghai Jiao Tong University)

  • Yang Zhou

    (Shanghai Jiao Tong University Affiliated Sixth People’s Hospital)

  • Jian-ren Gu

    (Shanghai Jiao Tong University)

  • Gary Gui-Shan Xiao

    (Dalian University of Technology
    Creighton University Medical Center)

  • Yong-wei Sun

    (Shanghai Jiao Tong University)

  • Jun Li

    (Shanghai Jiao Tong University)

  • Zhi-Gang Zhang

    (Shanghai Jiao Tong University)

Abstract

To explore the mechanism of coadaptation and the potential drivers of pancreatic ductal adenocarcinoma (PDAC) metastasis to the liver, we study key molecules involved in this process and their translational value. Premetastatic niche (PMN) and macrometastatic niche (MMN) formation in a mouse model is observed via CT combined with 3D organ reconstruction bioluminescence imaging, and then we screen slit guidance ligand 2 (SLIT2) and its receptor roundabout guidance receptor 1 (ROBO1) as important factors. After we confirm the expression and distribution of SLIT2 and ROBO1 in samples from PDAC patients and several mouse models, we discover that SLIT2-ROBO1-mediated coadaptation facilitated the implantation and outgrowth of PDAC disseminated tumour cells (DTCs) in the liver. We also demonstrate the dependence receptor (DR) characteristics of ROBO1 in a follow-up mechanistic study. A neutralizing antibody targeting ROBO1 significantly attenuate liver metastasis of PDAC by preventing the coadaptation effect. Thus, we demonstrate that coadaptation is supported by the DR characteristics in the PMN and MMN.

Suggested Citation

  • Qing Li & Xiao-Xin Zhang & Li-Peng Hu & Bo Ni & Dong-Xue Li & Xu Wang & Shu-Heng Jiang & Hui Li & Min-Wei Yang & Yong-Sheng Jiang & Chun-Jie Xu & Xue-Li Zhang & Yan-Li Zhang & Pei-Qi Huang & Qin Yang , 2023. "Coadaptation fostered by the SLIT2-ROBO1 axis facilitates liver metastasis of pancreatic ductal adenocarcinoma," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36521-0
    DOI: 10.1038/s41467-023-36521-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-36521-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-36521-0?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. Patrick Mehlen & Shahrooz Rabizadeh & Scott J. Snipas & Nuria Assa-Munt & Guy S. Salvesen & Dale E. Bredesen, 1998. "The DCC gene product induces apoptosis by a mechanism requiring receptor proteolysis," Nature, Nature, vol. 395(6704), pages 801-804, October.
    2. Andrew V. Biankin & Nicola Waddell & Karin S. Kassahn & Marie-Claude Gingras & Lakshmi B. Muthuswamy & Amber L. Johns & David K. Miller & Peter J. Wilson & Ann-Marie Patch & Jianmin Wu & David K. Chan, 2012. "Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes," Nature, Nature, vol. 491(7424), pages 399-405, November.
    3. Lin Zhang & Siyuan Zhang & Jun Yao & Frank J. Lowery & Qingling Zhang & Wen-Chien Huang & Ping Li & Min Li & Xiao Wang & Chenyu Zhang & Hai Wang & Kenneth Ellis & Mujeeburahiman Cheerathodi & Joseph H, 2015. "Microenvironment-induced PTEN loss by exosomal microRNA primes brain metastasis outgrowth," Nature, Nature, vol. 527(7576), pages 100-104, November.
    4. Jae W. Lee & Meredith L. Stone & Paige M. Porrett & Stacy K. Thomas & Chad A. Komar & Joey H. Li & Devora Delman & Kathleen Graham & Whitney L. Gladney & Xia Hua & Taylor A. Black & Austin L. Chien & , 2019. "Hepatocytes direct the formation of a pro-metastatic niche in the liver," Nature, Nature, vol. 567(7747), pages 249-252, March.
    5. Thomas R. Cox & Robin M. H. Rumney & Erwin M. Schoof & Lara Perryman & Anette M. Høye & Ankita Agrawal & Demelza Bird & Norain Ab Latif & Hamish Forrest & Holly R. Evans & Iain D. Huggins & Georgina L, 2015. "RETRACTED ARTICLE: The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase," Nature, Nature, vol. 522(7554), pages 106-110, June.
    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. 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.
    2. Sebastien Martinez & Shifei Wu & Michael Geuenich & Ahmad Malik & Ramona Weber & Tristan Woo & Amy Zhang & Gun Ho Jang & Dzana Dervovic & Khalid N. Al-Zahrani & Ricky Tsai & Nassima Fodil & Philippe G, 2024. "In vivo CRISPR screens reveal SCAF1 and USP15 as drivers of pancreatic cancer," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    3. Weili Ma & Maria Cecília Oliveira-Nunes & Ke Xu & Andrew Kossenkov & Benjamin C. Reiner & Richard C. Crist & James Hayden & Qing Chen, 2023. "Type I interferon response in astrocytes promotes brain metastasis by enhancing monocytic myeloid cell recruitment," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. James T. Topham & Erica S. Tsang & Joanna M. Karasinska & Andrew Metcalfe & Hassan Ali & Steve E. Kalloger & Veronika Csizmok & Laura M. Williamson & Emma Titmuss & Karina Nielsen & Gian Luca Negri & , 2022. "Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    5. Jérémy Guillot & Chloé Dominici & Adrien Lucchesi & Huyen Thi Trang Nguyen & Angélique Puget & Mélanie Hocine & Martha M. Rangel-Sosa & Milesa Simic & Jérémy Nigri & Fabienne Guillaumond & Martin Bigo, 2022. "Sympathetic axonal sprouting induces changes in macrophage populations and protects against pancreatic cancer," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    6. Misa Minegishi & Takahiro Kuchimaru & Kaori Nishikawa & Takayuki Isagawa & Satoshi Iwano & Kei Iida & Hiromasa Hara & Shizuka Miura & Marika Sato & Shigeaki Watanabe & Akifumi Shiomi & Yo Mabuchi & Hi, 2023. "Secretory GFP reconstitution labeling of neighboring cells interrogates cell–cell interactions in metastatic niches," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    7. Silje Kjølle & Kenneth Finne & Even Birkeland & Vandana Ardawatia & Ingeborg Winge & Sura Aziz & Gøril Knutsvik & Elisabeth Wik & Joao A. Paulo & Heidrun Vethe & Dimitrios Kleftogiannis & Lars A. Aksl, 2023. "Hypoxia induced responses are reflected in the stromal proteome of breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. Gaurav Mendiratta & Eugene Ke & Meraj Aziz & David Liarakos & Melinda Tong & Edward C. Stites, 2021. "Cancer gene mutation frequencies for the U.S. population," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    9. Stacy K. Thomas & Max M. Wattenberg & Shaanti Choi-Bose & Mark Uhlik & Ben Harrison & Heather Coho & Christopher R. Cassella & Meredith L. Stone & Dhruv Patel & Kelly Markowitz & Devora Delman & Micha, 2023. "Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Meng He & Yongxiang Liu & Song Chen & Haijing Deng & Cheng Feng & Shuang Qiao & Qifeng Chen & Yue Hu & Huiming Chen & Xun Wang & Xiongying Jiang & Xiaojun Xia & Ming Zhao & Ning Lyu, 2024. "Serum amyloid A promotes glycolysis of neutrophils during PD-1 blockade resistance in hepatocellular carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    11. Haochen Zhang & Elias-Ramzey Karnoub & Shigeaki Umeda & Ronan Chaligné & Ignas Masilionis & Caitlin A. McIntyre & Palash Sashittal & Akimasa Hayashi & Amanda Zucker & Katelyn Mullen & Jungeui Hong & A, 2023. "Application of high-throughput single-nucleus DNA sequencing in pancreatic cancer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Hongjuan Yao & Wenping Song & Rui Cao & Cheng Ye & Li Zhang & Hebing Chen & Junting Wang & Yuchen Shi & Rui Li & Yi Li & Xiujun Liu & Xiaofei Zhou & Rongguang Shao & Liang Li, 2022. "An EGFR/HER2-targeted conjugate sensitizes gemcitabine-sensitive and resistant pancreatic cancer through different SMAD4-mediated mechanisms," Nature Communications, Nature, vol. 13(1), pages 1-24, December.
    13. Eli Elyas & Alex Grimwood & Janine T Erler & Simon P Robinson & Thomas R Cox & Daniel Woods & Peter Clowes & Ramona De Luca & Franco Marinozzi & Jérémie Fromageau & Jeffrey C Bamber, 2017. "Multi-Channel Optical Coherence Elastography Using Relative and Absolute Shear-Wave Time of Flight," PLOS ONE, Public Library of Science, vol. 12(1), pages 1-18, January.
    14. Ilya G. Serebriiskii & Valery Pavlov & Rossella Tricarico & Grigorii Andrianov & Emmanuelle Nicolas & Mitchell I. Parker & Justin Newberg & Garrett Frampton & Joshua E. Meyer & Erica A. Golemis, 2022. "Comprehensive characterization of PTEN mutational profile in a series of 34,129 colorectal cancers," 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:14:y:2023:i:1:d:10.1038_s41467-023-36521-0. 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.