IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28340-6.html
   My bibliography  Save this article

Receptor-interacting protein kinase 2 (RIPK2) stabilizes c-Myc and is a therapeutic target in prostate cancer metastasis

Author

Listed:
  • Yiwu Yan

    (Cedars-Sinai Medical Center)

  • Bo Zhou

    (Cedars-Sinai Medical Center
    InterVenn Biosciences)

  • Chen Qian

    (Cedars-Sinai Medical Center)

  • Alex Vasquez

    (Cedars-Sinai Medical Center)

  • Mohini Kamra

    (Purdue University)

  • Avradip Chatterjee

    (Cedars-Sinai Medical Center)

  • Yeon-Joo Lee

    (Cedars-Sinai Medical Center)

  • Xiaopu Yuan

    (Cedars-Sinai Medical Center)

  • Leigh Ellis

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Dolores Vizio

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Edwin M. Posadas

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Natasha Kyprianou

    (Department of Urology, Icahn School of Medicine at Mount Sinai, New York)

  • Beatrice S. Knudsen

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    University of Utah)

  • Kavita Shah

    (Purdue University)

  • Ramachandran Murali

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Arkadiusz Gertych

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Sungyong You

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center)

  • Michael R. Freeman

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    University of California Los Angeles)

  • Wei Yang

    (Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    Cedars-Sinai Medical Center
    University of California Los Angeles)

Abstract

Despite progress in prostate cancer (PC) therapeutics, distant metastasis remains a major cause of morbidity and mortality from PC. Thus, there is growing recognition that preventing or delaying PC metastasis holds great potential for substantially improving patient outcomes. Here we show receptor-interacting protein kinase 2 (RIPK2) is a clinically actionable target for inhibiting PC metastasis. RIPK2 is amplified/gained in ~65% of lethal metastatic castration-resistant PC. Its overexpression is associated with disease progression and poor prognosis, and its genetic knockout substantially reduces PC metastasis. Multi-level proteomics analyses reveal that RIPK2 strongly regulates the stability and activity of c-Myc (a driver of metastasis), largely via binding to and activating mitogen-activated protein kinase kinase 7 (MKK7), which we identify as a direct c-Myc-S62 kinase. RIPK2 inhibition by preclinical and clinical drugs inactivates the noncanonical RIPK2/MKK7/c-Myc pathway and effectively impairs PC metastatic outgrowth. These results support targeting RIPK2 signaling to extend metastasis-free and overall survival.

Suggested Citation

  • Yiwu Yan & Bo Zhou & Chen Qian & Alex Vasquez & Mohini Kamra & Avradip Chatterjee & Yeon-Joo Lee & Xiaopu Yuan & Leigh Ellis & Dolores Vizio & Edwin M. Posadas & Natasha Kyprianou & Beatrice S. Knudse, 2022. "Receptor-interacting protein kinase 2 (RIPK2) stabilizes c-Myc and is a therapeutic target in prostate cancer metastasis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28340-6
    DOI: 10.1038/s41467-022-28340-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28340-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-28340-6?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. Mahmoud Ghandi & Franklin W. Huang & Judit Jané-Valbuena & Gregory V. Kryukov & Christopher C. Lo & E. Robert McDonald & Jordi Barretina & Ellen T. Gelfand & Craig M. Bielski & Haoxin Li & Kevin Hu & , 2019. "Next-generation characterization of the Cancer Cell Line Encyclopedia," Nature, Nature, vol. 569(7757), pages 503-508, May.
    2. Catherine S. Grasso & Yi-Mi Wu & Dan R. Robinson & Xuhong Cao & Saravana M. Dhanasekaran & Amjad P. Khan & Michael J. Quist & Xiaojun Jing & Robert J. Lonigro & J. Chad Brenner & Irfan A. Asangani & B, 2012. "The mutational landscape of lethal castration-resistant prostate cancer," Nature, Nature, vol. 487(7406), pages 239-243, July.
    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. Chih-Wei Chou & Chia-Nung Hung & Cheryl Hsiang-Ling Chiu & Xi Tan & Meizhen Chen & Chien-Chin Chen & Moawiz Saeed & Che-Wei Hsu & Michael A. Liss & Chiou-Miin Wang & Zhao Lai & Nathaniel Alvarez & Paw, 2023. "Phagocytosis-initiated tumor hybrid cells acquire a c-Myc-mediated quasi-polarization state for immunoevasion and distant dissemination," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    2. Nadege Gitego & Bogos Agianian & Oi Wei Mak & Vasantha Kumar MV & Emily H. Cheng & Evripidis Gavathiotis, 2023. "Chemical modulation of cytosolic BAX homodimer potentiates BAX activation and apoptosis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    3. C. Megan Young & Laurent Beziaud & Pierre Dessen & Angela Madurga Alonso & Albert Santamaria-Martínez & Joerg Huelsken, 2023. "Metabolic dependencies of metastasis-initiating cells in female breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Michael Fraser & Julie Livingstone & Jeffrey L. Wrana & Antonio Finelli & Housheng Hansen He & Theodorus van der Kwast & Alexandre R. Zlotta & Robert G. Bristow & Paul C. Boutros, 2021. "Somatic driver mutation prevalence in 1844 prostate cancers identifies ZNRF3 loss as a predictor of metastatic relapse," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. Fei Li & Yizhe Wang & Inah Hwang & Ja-Young Jang & Libo Xu & Zhong Deng & Eun Young Yu & Yiming Cai & Caizhi Wu & Zhenbo Han & Yu-Han Huang & Xiangao Huang & Ling Zhang & Jun Yao & Neal F. Lue & Paul , 2023. "Histone demethylase KDM2A is a selective vulnerability of cancers relying on alternative telomere maintenance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Yanli Liu & Zhong Wu & Jin Zhou & Dinesh K. A. Ramadurai & Katelyn L. Mortenson & Estrella Aguilera-Jimenez & Yifei Yan & Xiaojun Yang & Alison M. Taylor & Katherine E. Varley & Jason Gertz & Peter S., 2021. "A predominant enhancer co-amplified with the SOX2 oncogene is necessary and sufficient for its expression in squamous cancer," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    7. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    8. Sandra M. Rocha & Sílvia Socorro & Luís A. Passarinha & Cláudio J. Maia, 2022. "Comprehensive Landscape of STEAP Family Members Expression in Human Cancers: Unraveling the Potential Usefulness in Clinical Practice Using Integrated Bioinformatics Analysis," Data, MDPI, vol. 7(5), pages 1-48, May.
    9. Xiao Chen & Yinglu Li & Fang Zhu & Xinjing Xu & Brian Estrella & Manuel A. Pazos & John T. McGuire & Dimitris Karagiannis & Varun Sahu & Mustafo Mustafokulov & Claudio Scuoppo & Francisco J. Sánchez-R, 2023. "Context-defined cancer co-dependency mapping identifies a functional interplay between PRC2 and MLL-MEN1 complex in lymphoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    10. Johanna Zerbib & Marica Rosaria Ippolito & Yonatan Eliezer & Giuseppina Feudis & Eli Reuveni & Anouk Savir Kadmon & Sara Martin & Sonia Viganò & Gil Leor & James Berstler & Julia Muenzner & Michael Mü, 2024. "Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    11. Ruitong Li & Olaf Klingbeil & Davide Monducci & Michael J. Young & Diego J. Rodriguez & Zaid Bayyat & Joshua M. Dempster & Devishi Kesar & Xiaoping Yang & Mahdi Zamanighomi & Christopher R. Vakoc & Ta, 2022. "Comparative optimization of combinatorial CRISPR screens," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    12. 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.
    13. Hsiao-Yun Chen & Yavuz T. Durmaz & Yixiang Li & Amin H. Sabet & Amir Vajdi & Thomas Denize & Emily Walton & Yasmin Nabil Laimon & John G. Doench & Navin R. Mahadevan & Julie-Aurore Losman & David A. B, 2022. "Regulation of neuroendocrine plasticity by the RNA-binding protein ZFP36L1," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    14. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    15. Lorenza Garribba & Giuseppina De Feudis & Valentino Martis & Martina Galli & Marie Dumont & Yonatan Eliezer & René Wardenaar & Marica Rosaria Ippolito & Divya Ramalingam Iyer & Andréa E. Tijhuis & Dia, 2023. "Short-term molecular consequences of chromosome mis-segregation for genome stability," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    16. Jiawen Bu & Yixiao Zhang & Sijin Wu & Haonan Li & Lisha Sun & Yang Liu & Xudong Zhu & Xinbo Qiao & Qingtian Ma & Chao Liu & Nan Niu & Jinqi Xue & Guanglei Chen & Yongliang Yang & Caigang Liu, 2023. "KK-LC-1 as a therapeutic target to eliminate ALDH+ stem cells in triple negative breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    17. Shixiang Wang & Chen-Yi Wu & Ming-Ming He & Jia-Xin Yong & Yan-Xing Chen & Li-Mei Qian & Jin-Ling Zhang & Zhao-Lei Zeng & Rui-Hua Xu & Feng Wang & Qi Zhao, 2024. "Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    18. Shideh Mirhadi & Shirley Tam & Quan Li & Nadeem Moghal & Nhu-An Pham & Jiefei Tong & Brian J. Golbourn & Jonathan R. Krieger & Paul Taylor & Ming Li & Jessica Weiss & Sebastiao N. Martins-Filho & Vibh, 2022. "Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    19. Tian-Yu Song & Min Long & Hai-Xin Zhao & Miao-Wen Zou & Hong-Jie Fan & Yang Liu & Chen-Lu Geng & Min-Fang Song & Yu-Feng Liu & Jun-Yi Chen & Yu-Lin Yang & Wen-Rong Zhou & Da-Wei Huang & Bo Peng & Zhen, 2021. "Tumor evolution selectively inactivates the core microRNA machinery for immune evasion," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    20. Ziad Ibrahim & Tao Wang & Olivier Destaing & Nicola Salvi & Naghmeh Hoghoughi & Clovis Chabert & Alexandra Rusu & Jinjun Gao & Leonardo Feletto & Nicolas Reynoird & Thomas Schalch & Yingming Zhao & Ma, 2022. "Structural insights into p300 regulation and acetylation-dependent genome organisation," Nature Communications, Nature, vol. 13(1), pages 1-23, 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_s41467-022-28340-6. 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.