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Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1

Author

Listed:
  • Yu-Xiong Feng

    (Whitehead Institute for Biomedical Research)

  • Dexter X. Jin

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Ethan S. Sokol

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Ferenc Reinhardt

    (Whitehead Institute for Biomedical Research)

  • Daniel H. Miller

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Piyush B. Gupta

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology
    David H. Koch Institute for Integrative Cancer Research
    Harvard Stem Cell Institute)

Abstract

PERK signaling is required for cancer invasion and there is interest in targeting this pathway for therapy. Unfortunately, chemical inhibitors of PERK’s kinase activity cause on-target side effects that have precluded their further development. One strategy for resolving this difficulty would be to target downstream components of the pathway that specifically mediate PERK’s pro-invasive and metastatic functions. Here we identify the transcription factor CREB3L1 as an essential mediator of PERK’s pro-metastatic functions in breast cancer. CREB3L1 acts downstream of PERK, specifically in the mesenchymal subtype of triple-negative tumors, and its inhibition by genetic or pharmacological methods suppresses cancer cell invasion and metastasis. In patients with this tumor subtype, CREB3L1 expression is predictive of distant metastasis. These findings establish CREB3L1 as a key downstream mediator of PERK-driven metastasis and a druggable target for breast cancer therapy.

Suggested Citation

  • Yu-Xiong Feng & Dexter X. Jin & Ethan S. Sokol & Ferenc Reinhardt & Daniel H. Miller & Piyush B. Gupta, 2017. "Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01052-y
    DOI: 10.1038/s41467-017-01052-y
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    Cited by:

    1. Rohit Arora & Christian Cao & Mehul Kumar & Sarthak Sinha & Ayan Chanda & Reid McNeil & Divya Samuel & Rahul K. Arora & T. Wayne Matthews & Shamir Chandarana & Robert Hart & Joseph C. Dort & Jeff Bier, 2023. "Spatial transcriptomics reveals distinct and conserved tumor core and edge architectures that predict survival and targeted therapy response," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    2. Brooke D. Huisman & Ning Guan & Timo Rückert & Lee Garner & Nishant K. Singh & Andrew J. McMichael & Geraldine M. Gillespie & Chiara Romagnani & Michael E. Birnbaum, 2023. "High-throughput characterization of HLA-E-presented CD94/NKG2x ligands reveals peptides which modulate NK cell activation," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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