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ATF6α inhibits ΔNp63α expression to promote breast cancer metastasis by the GRP78-AKT1-FOXO3a signaling

  • 0Department of Cardiothoracic Surgery, School of Clinical Medicine and The First Affiliated Hospital of Chengdu Medical College, Chengdu, China.
Cell Death & Disease +

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April 13, 2025

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April 13, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Endoplasmic reticulum (ER) stress promotes breast cancer metastasis by activating ATF6α, which suppresses the metastasis suppressor ΔNp63α. Targeting the ATF6α-GRP78-AKT1-FOXO3a pathway offers a potential therapeutic strategy for breast cancer.

Area Of Science

  • Oncology
  • Molecular Biology
  • Cellular Stress Response

Background

  • Endoplasmic reticulum (ER) stress is implicated in cancer progression, but its role in metastasis is not fully understood.
  • Identifying molecular mechanisms linking ER stress to tumor spread is crucial for developing effective treatments.

Purpose Of The Study

  • To elucidate the molecular mechanisms by which ER stress drives breast cancer cell migration and metastasis.
  • To investigate the role of the ATF6α pathway in regulating metastasis suppressor ΔNp63α.

Main Methods

  • Investigated the ATF6α signaling pathway in breast cancer cells.
  • Utilized molecular biology techniques including gene knockdown and pharmacological inhibition.
  • Analyzed patient tumor tissues for expression levels of key proteins.

Main Results

  • ER stress-activated ATF6α downregulates metastasis suppressor ΔNp63α via the GRP78-AKT1-FOXO3a axis.
  • AKT1 inhibition upregulates ΔNp63α and suppresses metastasis in vivo.
  • Reduced TP63 and FOXO3a, and elevated ATF6 and GRP78 correlate with poor prognosis in breast cancer patients.

Conclusions

  • The ATF6α-GRP78-AKT1-FOXO3a axis is a key mediator of ER stress-induced downregulation of ΔNp63α.
  • This pathway represents a potential therapeutic target for inhibiting breast cancer metastasis.

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