IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-30159-0.html
   My bibliography  Save this article

Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer

Author

Listed:
  • Aitor Almanza

    (National University of Ireland
    National University of Ireland)

  • Katarzyna Mnich

    (National University of Ireland
    National University of Ireland)

  • Arnaud Blomme

    (CRUK Beatson Institute)

  • Claire M. Robinson

    (National University of Ireland
    National University of Ireland)

  • Giovanny Rodriguez-Blanco

    (CRUK Beatson Institute)

  • Sylwia Kierszniowska

    (metaSysX GmbH)

  • Eoghan P. McGrath

    (National University of Ireland
    National University of Ireland)

  • Matthieu Gallo

    (University of Rennes
    Centre de lutte contre le cancer Eugène Marquis)

  • Eleftherios Pilalis

    (e-NIOS Applications PC)

  • Johannes V. Swinnen

    (KU Leuven Cancer Institute)

  • Aristotelis Chatziioannou

    (e-NIOS Applications PC
    Biomedical Research Foundation of the Academy of Athens)

  • Eric Chevet

    (University of Rennes
    Centre de lutte contre le cancer Eugène Marquis)

  • Adrienne M. Gorman

    (National University of Ireland
    National University of Ireland)

  • Afshin Samali

    (National University of Ireland
    National University of Ireland)

Abstract

IRE1α is constitutively active in several cancers and can contribute to cancer progression. Activated IRE1α cleaves XBP1 mRNA, a key step in production of the transcription factor XBP1s. In addition, IRE1α cleaves select mRNAs through regulated IRE1α-dependent decay (RIDD). Accumulating evidence implicates IRE1α in the regulation of lipid metabolism. However, the roles of XBP1s and RIDD in this process remain ill-defined. In this study, transcriptome and lipidome profiling of triple negative breast cancer cells subjected to pharmacological inhibition of IRE1α reveals changes in lipid metabolism genes associated with accumulation of triacylglycerols (TAGs). We identify DGAT2 mRNA, encoding the rate-limiting enzyme in TAG biosynthesis, as a RIDD target. Inhibition of IRE1α, leads to DGAT2-dependent accumulation of TAGs in lipid droplets and sensitizes cells to nutritional stress, which is rescued by treatment with the DGAT2 inhibitor PF-06424439. Our results highlight the importance of IRE1α RIDD activity in reprograming cellular lipid metabolism.

Suggested Citation

  • Aitor Almanza & Katarzyna Mnich & Arnaud Blomme & Claire M. Robinson & Giovanny Rodriguez-Blanco & Sylwia Kierszniowska & Eoghan P. McGrath & Matthieu Gallo & Eleftherios Pilalis & Johannes V. Swinnen, 2022. "Regulated IRE1α-dependent decay (RIDD)-mediated reprograming of lipid metabolism in cancer," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30159-0
    DOI: 10.1038/s41467-022-30159-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-30159-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-30159-0?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. Mengle Shao & Bo Shan & Yang Liu & Yiping Deng & Cheng Yan & Ying Wu & Ting Mao & Yifu Qiu & Yubo Zhou & Shan Jiang & Weiping Jia & Jingya Li & Jia Li & Liangyou Rui & Liu Yang & Yong Liu, 2014. "Hepatic IRE1α regulates fasting-induced metabolic adaptive programs through the XBP1s–PPARα axis signalling," Nature Communications, Nature, vol. 5(1), pages 1-12, May.
    2. Arnaud Blomme & Catriona A. Ford & Ernest Mui & Rachana Patel & Chara Ntala & Lauren E. Jamieson & Mélanie Planque & Grace H. McGregor & Paul Peixoto & Eric Hervouet & Colin Nixon & Mark Salji & Luke , 2020. "2,4-dienoyl-CoA reductase regulates lipid homeostasis in treatment-resistant prostate cancer," Nature Communications, Nature, vol. 11(1), pages 1-17, December.
    3. Xi Chen & Dimitrios Iliopoulos & Qing Zhang & Qianzi Tang & Matthew B. Greenblatt & Maria Hatziapostolou & Elgene Lim & Wai Leong Tam & Min Ni & Yiwen Chen & Junhua Mai & Haifa Shen & Dorothy Z. Hu & , 2014. "XBP1 promotes triple-negative breast cancer by controlling the HIF1α pathway," Nature, Nature, vol. 508(7494), pages 103-107, April.
    4. Susan E. Logue & Eoghan P. McGrath & Patricia Cleary & Stephanie Greene & Katarzyna Mnich & Aitor Almanza & Eric Chevet & Róisín M. Dwyer & Anup Oommen & Patrick Legembre & Florence Godey & Emma C. Ma, 2018. "Inhibition of IRE1 RNase activity modulates the tumor cell secretome and enhances response to chemotherapy," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    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. Michael J. P. Crowley & Bhavneet Bhinder & Geoffrey J. Markowitz & Mitchell Martin & Akanksha Verma & Tito A. Sandoval & Chang-Suk Chae & Shira Yomtoubian & Yang Hu & Sahil Chopra & Diamile A. Tavarez, 2023. "Tumor-intrinsic IRE1α signaling controls protective immunity in lung cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Jiang-jiang Li & Tiantian Yu & Peiting Zeng & Jingyu Tian & Panpan Liu & Shuang Qiao & Shijun Wen & Yumin Hu & Qiao Liu & Wenhua Lu & Hui Zhang & Peng Huang, 2024. "Wild-type IDH2 is a therapeutic target for triple-negative breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Fei Xiao & Haizhou Jiang & Zi Li & Xiaoxue Jiang & Shanghai Chen & Yuguo Niu & Hanrui Yin & Yousheng Shu & Bo Peng & Wei Lu & Xiaoying Li & Zhigang Li & Shujue Lan & Xiaoyan Xu & Feifan Guo, 2023. "Reduced hepatic bradykinin degradation accounts for cold-induced BAT thermogenesis and WAT browning in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Xinyuan Lei & Hsinyu Lin & Jieqi Wang & Zhanpeng Ou & Yi Ruan & Ananthan Sadagopan & Weixiong Chen & Shule Xie & Baisheng Chen & Qunxing Li & Jue Wang & Huayue Lin & Xiaofeng Zhu & Xiaoqing Yuan & Tia, 2022. "Mitochondrial fission induces immunoescape in solid tumors through decreasing MHC-I surface expression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Jing Yan & Yuemei Zhang & Hairong Yu & Yicen Zong & Daixi Wang & Jiangfei Zheng & Li Jin & Xiangtian Yu & Caizhi Liu & Yi Zhang & Feng Jiang & Rong Zhang & Xiangnan Fang & Ting Xu & Mingyu Li & Jianzh, 2022. "GPSM1 impairs metabolic homeostasis by controlling a pro-inflammatory pathway in macrophages," Nature Communications, Nature, vol. 13(1), pages 1-22, December.
    6. Bo Wen & Bing Zhang, 2023. "PepQuery2 democratizes public MS proteomics data for rapid peptide searching," Nature Communications, Nature, vol. 14(1), pages 1-13, 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_s41467-022-30159-0. 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.