Cell Death Discovery (Jul 2024)

Endoplasmic reticulum stress—a key guardian in cancer

  • Wenlong Zhang,
  • Yidan Shi,
  • Linda Oyang,
  • Shiwen Cui,
  • Shizhen Li,
  • Jinyun Li,
  • Lin Liu,
  • Yun Li,
  • Mingjing Peng,
  • Shiming Tan,
  • Longzheng Xia,
  • Jinguan Lin,
  • Xuemeng Xu,
  • Nayiyuan Wu,
  • Qiu Peng,
  • Yanyan Tang,
  • Xia Luo,
  • Qianjin Liao,
  • Xianjie Jiang,
  • Yujuan Zhou

DOI
https://doi.org/10.1038/s41420-024-02110-3
Journal volume & issue
Vol. 10, no. 1
pp. 1 – 16

Abstract

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Abstract Endoplasmic reticulum stress (ERS) is a cellular stress response characterized by excessive contraction of the endoplasmic reticulum (ER). It is a pathological hallmark of many diseases, such as diabetes, obesity, and neurodegenerative diseases. In the unique growth characteristic and varied microenvironment of cancer, high levels of stress are necessary to maintain the rapid proliferation and metastasis of tumor cells. This process is closely related to ERS, which enhances the ability of tumor cells to adapt to unfavorable environments and promotes the malignant progression of cancer. In this paper, we review the roles and mechanisms of ERS in tumor cell proliferation, apoptosis, metastasis, angiogenesis, drug resistance, cellular metabolism, and immune response. We found that ERS can modulate tumor progression via the unfolded protein response (UPR) signaling of IRE1, PERK, and ATF6. Targeting the ERS may be a new strategy to attenuate the protective effects of ERS on cancer. This manuscript explores the potential of ERS-targeted therapies, detailing the mechanisms through which ERS influences cancer progression and highlighting experimental and clinical evidence supporting these strategies. Through this review, we aim to deepen our understanding of the role of ER stress in cancer development and provide new insights for cancer therapy.