J Breast Cancer.  2018 Dec;21(4):354-362. 10.4048/jbc.2018.21.e51.

New Insights into the Role of Endoplasmic Reticulum Stress in Breast Cancer Metastasis

• Han CC
• Wan FS

• KMID: 2429813
• DOI: http://doi.org/10.4048/jbc.2018.21.e51

Abstract

Cellular stress severely disrupts endoplasmic reticulum (ER) function, leading to the abnormal accumulation of unfolded or misfolded proteins in the ER and subsequent development of endoplasmic reticulum stress (ERS). To accommodate the occurrence of ERS, cells have evolved a highly conserved, self-protecting signal transduction pathway called the unfolded protein response. Notably, ERS signaling is involved in the development of a variety of diseases and is closely related to tumor development, particularly in breast cancer. This review discusses recent research regarding associations between ERS and tumor metastasis. The information presented here will help researchers elucidate the precise mechanisms underlying ERS-mediated tumor metastasis and provide new directions for tumor therapies.

Keyword

Breast neoplasms; Endoplasmic reticulum stress; Neoplasm metastasis; Unfolded protein response

MeSH Terms

Breast Neoplasms*
Breast*
Endoplasmic Reticulum Stress*
Endoplasmic Reticulum*
Neoplasm Metastasis*
Signal Transduction
Unfolded Protein Response

Figure

• 

  Figure 1 Endoplasmic reticulum stress (ERS) and breast cancer metastasis. Glucose-regulated protein 78 (GRP78) dissociates from ERS transducers, including inositol-requiring enzyme 1 (IRE1), protein kinase R-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6 (ATF6), when unfolded or misfolded proteins accumulate in the endoplasmic reticulum lumen. ERS regulates tumour metastasis mainly through matrix metalloproteinases (MMPs), epithelial-mesenchymal transition (EMT), autophagy, reactive oxygen species (ROS), and other transcription factors.eIF2α=eukaryotic translation initiation factor 2α; XBP1=X-box-binding protein 1; S1P=site 1 protease; S2P=site 2 protease; ATF4=activating transcription factor 4; JNK=c-Jun N-terminal kinase.

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