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Updated: Feb 20, 2026

Impedance-based Real-time Measurement of Cancer Cell Migration and Invasion
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Cancer-specific PERK signaling drives invasion and metastasis through CREB3L1

Yu-Xiong Feng1, Dexter X Jin1,2, Ethan S Sokol1,2

  • 1Whitehead Institute for Biomedical Research, 455 Main Street, Cambridge, MA, 02142, USA.

Nature Communications
|October 24, 2017
PubMed

Insights

Targeting the PERK pathway in breast cancer is promising, but inhibitors cause side effects. Researchers identified CREB3L1 as a key downstream mediator that drives metastasis, offering a new therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • PERK signaling is crucial for cancer invasion and metastasis.
  • Existing PERK kinase inhibitors cause significant side effects, limiting their therapeutic use.
  • Targeting downstream effectors of PERK offers a strategy to mitigate side effects and specifically inhibit pro-metastatic functions.

Purpose of the Study:

  • To identify downstream mediators of PERK signaling responsible for breast cancer invasion and metastasis.
  • To evaluate the therapeutic potential of targeting these downstream mediators.

Main Methods:

  • Utilized genetic and pharmacological inhibition methods.
  • Investigated the role of transcription factor CREB3L1 in PERK-driven metastasis.
  • Analyzed CREB3L1 expression in patient tumor samples.

Main Results:

  • Identified CREB3L1 as an essential mediator of PERK's pro-metastatic functions in breast cancer.
  • CREB3L1 acts downstream of PERK, particularly in the mesenchymal subtype of triple-negative breast tumors.
  • Inhibition of CREB3L1 suppressed cancer cell invasion and metastasis.
  • CREB3L1 expression levels predicted distant metastasis in patients with this tumor subtype.

Conclusions:

  • CREB3L1 is a key downstream effector of PERK-mediated metastasis in specific breast cancer subtypes.
  • CREB3L1 represents a druggable target for developing novel breast cancer therapies.
  • Targeting CREB3L1 may offer a way to inhibit metastasis with potentially fewer side effects than direct PERK inhibition.

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