The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis

Hendershot, Linda M.; Buck, Teresa M.; Brodsky, Jeffrey L.

doi:10.1016/j.jmb.2023.168418

Cited by 7 publications

(4 citation statements)

References 242 publications

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“…Activation of this pathway helps limit proteotoxic stress by increasing the expression of chaperones such as heat shock proteins (e.g. HSP90 family proteins) and, in the case of XBP1, protein disulphide isomerases ( Hendershot et al, 2023 ). In prostate cancer, the androgen receptor (AR) was shown to transcriptionally activate IRE1α and XBP1 to sustain tumorigenesis through increased rates of anabolic metabolism and lipid turnover ( Sheng et al, 2015 ).…”

Section: Modulation Of Er-to-golgi Trafficking Drives Cancer Progressionmentioning

confidence: 99%

Adaptations of membrane trafficking in cancer and tumorigenesis

Evergren,

Mills,

Kennedy

2024

Journal of Cell Science

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Membrane trafficking, a fundamental cellular process encompassing the transport of molecules to specific organelles, endocytosis at the plasma membrane and protein secretion, is crucial for cellular homeostasis and signalling. Cancer cells adapt membrane trafficking to enhance their survival and metabolism, and understanding these adaptations is vital for improving patient responses to therapy and identifying therapeutic targets. In this Review, we provide a concise overview of major membrane trafficking pathways and detail adaptations in these pathways, including COPII-dependent endoplasmic reticulum (ER)-to-Golgi vesicle trafficking, COPI-dependent retrograde Golgi-to-ER trafficking and endocytosis, that have been found in cancer. We explore how these adaptations confer growth advantages or resistance to cell death and conclude by discussing the potential for utilising this knowledge in developing new treatment strategies and overcoming drug resistance for cancer patients.

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Section: Modulation Of Er-to-golgi Trafficking Drives Cancer Progressionmentioning

confidence: 99%

Adaptations of membrane trafficking in cancer and tumorigenesis

Evergren,

Mills,

Kennedy

2024

Journal of Cell Science

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“…the endoplasmic reticulum and even in the mitochondria. However, the chaperones of interest in this study are the HSPs that reside in the lumen of the endoplasmic reticulum (ER) where they perform several important functions related to proteostasis and cellular protection [9]. The rough endoplasmic reticulum (ER), an organelle connected to the nuclear membrane, is the site of most protein synthesis, translation, folding and quality control processes.…”

Section: Introductionmentioning

confidence: 99%

“…The rough endoplasmic reticulum (ER), an organelle connected to the nuclear membrane, is the site of most protein synthesis, translation, folding and quality control processes. These processes must be organized and harmonious so that they can process different spatial conformations of specific proteins, but they must also be sensitive enough to recognize that an unrecoverable protein must be degraded, a task up to the HSPs [9].…”

Section: Introductionmentioning

confidence: 99%

“…Three major groups of chaperones play a role in the folding and degradation (ubiquitination) mechanism of ER proteins: heat shock proteins (e.g., HSP40, HSP60, HSP70, and HSP90), ER lectins (e.g., calnexin, calreticulin), and thiol oxidoreductases (e.g., Protein Disulfide Isomerase -PDI) [9]. The pathophysiology of diseases such as cystic fibrosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, Huntington's disease, diabetes mellitus, obesity, cardiovascular disease, and even some types of cancer are related to poor functioning of the Endoplasmic Reticulum Quality Control -ERQC.…”

Section: Introductionmentioning

confidence: 99%

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Colorectal cancer and endoplasmic reticulum stress – potential targets for therapeutic compounds

Sobrinho,

Almeida,

Selzler

et al. 2024

J Pre Clin Clin Res.

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Introduction and Objective.Colorectal cancer (CRC), a malignant neoplasm of the gastrointestinal tract, affects the colon and rectum, its incidence is high, being the third most common neoplasm in men, with two million cases/year and survival <70%/5 years. The pathophysiology and progression of CRC are closely related to endoplasmic reticulum stress (ERE) and the unfolded or misfolded protein response (UPR). ERE can be triggered by various oxidative stress and inflammation factors with high UPR load followed by physicochemical and conformational interactions. The aim of the review is to present recent evidence on the relationships between endoplasmic reticulum stress, unfolded protein response and colorectal cancer. Review Methods. An expanded integrative review was carried out of scientific information from PubMed, LILACS and SciELO health databases. Articles containing key words were selected for abstract fast readings, followed by full text selections of works containing targeted subjects. From a total of 198 articles, 96 were selected (92% ≤ 8 years) for inclusion in the review. Brief description of the state of knowledge. New developments in CRC research are presented within approaches to molecular pathophysiological pathways, a spectrum of therapeutic targets and suggestive diets with a view of intestinal microbiota and dysbiosis, considering progression stages and evidences correlating CRC to socio-environmental and innate or acquired genetic load. Putative CRC target compounds and drugs, such as Aspirin, Fucoidan, PERK inhibitor, antimicrobial and current natural antioxidants are briefly presented and discussed. Summary. Chaperone proteins may accumulate misfolded proteins in the endoplasmic reticulum, causing disruption of ERE proteostasis. While CRC progression is closely related to these signaling pathways, a better understanding is vital for new target-specific anticarcinogenic molecules.

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