The Unfolded Protein Response in Breast Cancer

McGrath, Eoghan P.; Logue, Susan E.; Mnich, Katarzyna; Deegan, Shane; Jäger, Richard; Gorman, Adrienne M.; Samali, Afshin

doi:10.3390/cancers10100344

Cited by 65 publications

(55 citation statements)

References 145 publications

(169 reference statements)

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“…The ER stress mediated by taxane could induce apoptosis of cancer cells [26]. In this process, unfolded protein response (UPR) signaling pathway could weaken ER stress to maintain ER homeostasis and help cells survive [27]. Researchers had demonstrated that AGR2 could bind GRP78 which was a central trigger of UPR.…”

Section: Discussionmentioning

confidence: 99%

Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response

Shao

Zhang

et al. 2020

Cancer Res Treat

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Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression. Materials and Methods AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3's correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3's impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected. Results AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines. Conclusion AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.

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Section: Discussionmentioning

confidence: 99%

Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response

Shao

Zhang

et al. 2020

Cancer Res Treat

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“…Many different perturbations can alter the function of the ER leading to unfolding or misfolding of proteins in the ER. This condition is referred to as ER stress [133,134]. The ER creates a series of adaptive mechanisms in order to prevent cell death complications and these together are referred to as unfolded protein response (UPR) [133,135].…”

Section: Unfolded Protein Response Pathwaymentioning

confidence: 99%

“…Activation of IRE1 involves first dissociating itself from Grp78. Then, IRE1 undergoes dimerization, oligomerization, and trans-autophosphorylation, which leads to conformational changes and activation of its RNase domain [133,134]. Activated IRE1 excises a 26nucleotide intron region from mRNA that encodes the transcription factor X-box binding protein 1 (XBP1).…”

Section: Unfolded Protein Response Pathwaymentioning

confidence: 99%

The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections

Mehrbod¹,

et al. 2019

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Virus infection induces different cellular responses in infected cells. These include cellular stress responses like autophagy and unfolded protein response (UPR). Both autophagy and UPR are connected to programed cell death I (apoptosis) in chronic stress conditions to regulate cellular homeostasis via Bcl2 family proteins, CHOP and Beclin-1. In this review article we first briefly discuss arboviruses, influenza virus, and HIV and then describe the concepts of apoptosis, autophagy, and UPR. Finally, we focus upon how apoptosis, autophagy, and UPR are involved in the regulation of cellular responses to arboviruses, influenza virus and HIV infections.

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Section: Clinicopathological Parametermentioning

confidence: 99%

“…In recent years, attention has been focused on the endoplasmic reticulum stress response, including UPR in cancer cells (19). UPR is involved in protein-folding homeostasis against various stresses and is enhanced in cancer cells, resulting in cancer progression (19). As UPR activates endoplasmic reticulum chaperones that stabilize protein-folding to promote cancer cell survival, proliferation, angiogenesis, metastasis, and therapy resistance (20), UPR-related pathways or molecules have been considered attractive candidates for novel biomarkers or therapeutic targets.…”

Section: Clinicopathological Parametermentioning

confidence: 99%

MZB1 expression indicates poor prognosis in estrogen receptor‑positive breast cancer

et al. 2020

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Breast cancer (BC) is the most common malignant tumor in females. Development of novel biomarkers or therapeutic targets may contribute toward the improvement of a patient's prognosis. Marginal zone B and B1 cell-specific protein (MZB1) is an unfolded protein response-related chaperone and mainly exists in the endoplasmic reticulum of B lymphocytes, although little is known regarding its role in BC cells. The present study aimed to investigate the significance of MZB1 expression in BC. To begin with, MZB1 mRNA expression levels in 13 BC cell lines and two non-cancerous mammary cell lines were evaluated. Next, mRNA and protein expression of MZB1 in BC patient tumor specimens was evaluated to assess the association between expression and clinicopathological factors or prognosis. MZB1 mRNA expression levels were detectable in four estrogen receptor (ER)-positive BC cell lines. When ratios of MZB1 mRNA expression levels between BC and non-cancerous specimens were evaluated, patients with stage III disease exhibited a higher ratio than patients with stage 0/I/II disease (P=0.009). Using immunohistochemistry, patients with ER-positive BC more frequently expressed MZB1, compared with patients with ER-negative BC (P=0.003). In patients with ER-positive BC, patients with MZB1-positive BC experienced shorter disease-free survival (DFS) times than patients with negative BC (P=0.026). Multivariate analysis of DFS demonstrated that MZB1 positivity was an independent prognostic factor (P=0.022). The results of the present study suggested that MZB1 expression may be associated with a more advanced stage of BC. Furthermore, in patients with ER-positive BC, MZB1 may be a potential prognostic marker.

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The Unfolded Protein Response in Breast Cancer

Cited by 65 publications

References 145 publications

Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response

Anterior Gradient 3 Promotes Breast Cancer Development and Chemotherapy Response

The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections

MZB1 expression indicates poor prognosis in estrogen receptor‑positive breast cancer

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