Inhibition of ERO1L induces autophagy and apoptosis via endoplasmic reticulum stress in colorectal cancer.

Cell Signal

Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital Bonn, 53127 Bonn, Germany. Electronic address:

Published: December 2024

Colorectal cancer (CRC) is one of the most common types of cancer with high incidence and mortality. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) is overexpressed in CRC. This study aims to explore the role of ERO1L in CRC progression and evaluate the anti-tumor efficacy of the combination treatment of ERO1L inhibition with endoplasmic reticulum (ER) stress-inducing therapies. Herein, we found that ERO1L was elevated in CRC cell lines and patients. ER stress upregulated the expression of ERO1L, and ERO1L deficiency induced ER stress in CRC. ERO1L knockdown increased the susceptibility of CRC cells to ER stress. ERO1L contributed to the malignant phenotypes of CRC cells. Inhibition of ERO1L induced autophagy and caspase-dependent apoptosis by the induction of ER stress in CRC cells. Mechanically, the ERK1/2 pathway was involved in ERO1L knockdown-mediated apoptosis and autophagy. Combination treatment of ERO1L inhibition with ER stress-inducing agents, such as unfolded protein response (UPR)-targeting inhibitors and proteasome inhibitors, demonstrated enhanced anti-tumor capacity. In conclusion, ERO1L is overexpressed in CRC, and ERO1L deficiency induces apoptosis and autophagy via ER stress. ERO1L inhibition combined with ER stress-inducing therapies exhibits more effective anti-tumor activity against CRC. ERO1L may serve as a biomarker and therapeutic target for CRC treatment.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2024.111560DOI Listing

Publication Analysis

Top Keywords

ero1l
15
endoplasmic reticulum
12
ero1l inhibition
12
crc ero1l
12
crc cells
12
crc
11
inhibition ero1l
8
colorectal cancer
8
ero1l overexpressed
8
overexpressed crc
8

Similar Publications

Inhibition of ERO1L induces autophagy and apoptosis via endoplasmic reticulum stress in colorectal cancer.

Cell Signal

December 2024

Department of Integrated Oncology, Center for Integrated Oncology (CIO), University Hospital Bonn, 53127 Bonn, Germany. Electronic address:

Colorectal cancer (CRC) is one of the most common types of cancer with high incidence and mortality. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1L) is overexpressed in CRC. This study aims to explore the role of ERO1L in CRC progression and evaluate the anti-tumor efficacy of the combination treatment of ERO1L inhibition with endoplasmic reticulum (ER) stress-inducing therapies.

View Article and Find Full Text PDF

ERO1A inhibition mitigates neuronal ER stress and ameliorates UBQLN2 phenotypes in Drosophila melanogaster.

Prog Neurobiol

November 2024

Drosophila Centre for Human Diseases and Drug Discovery (DHD), Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. Electronic address:

Article Synopsis
  • * Genetic suppression or inhibition of ERO1A in Drosophila models provided neuroprotection and increased lifespan under ER stress conditions.
  • * Using the inhibitor EN460 improved motor functions and NMJ structure in models of UBQLN2-related pathology, highlighting ERO1A's potential as a therapeutic target for ER stress-related neurodegenerative diseases.
View Article and Find Full Text PDF

Transcriptomics analysis reveals distinct mechanism of breast cancer stem cells regulation in mammospheres from MCF-7 and T47D cells.

Heliyon

January 2024

Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, 55281, Yogyakarta, Indonesia.

Luminal A breast cancer, constituting 70 % of breast cancer cases, presents a challenge due to the development of resistance and recurrence caused by breast cancer stem cells (BCSC). Luminal breast tumors are characterized by expression, a tumor suppressor gene involved in maintaining stem cell attributes in cancer. Although a previous study successfully developed mammospheres (MS) from MCF-7 (with wild-type ) and T47D (with mutant ) luminal breast cancer cells for BCSC enrichment, their transcriptomic profiles remain unclear.

View Article and Find Full Text PDF
Article Synopsis
  • Di-2-ethylhexyl phthalate (DEHP) is an endocrine disruptor that causes reproductive toxicity, potentially through mechanisms involving apoptosis and ER stress.
  • In a study using rats, exposure to DEHP led to testicular injury and altered gene expression linked to pathways for apoptosis, PPARα, and ER stress.
  • The research suggests that mitochondrial dysfunction and a feedback loop involving ER stress and reactive oxygen species (ROS) contribute significantly to DEHP-induced cell death, highlighting the role of PPARα activation.
View Article and Find Full Text PDF

Background: High throughput gene expression profiling is a valuable tool in providing insight into the molecular mechanism of human diseases. Hypoxia- and lactate metabolism-related genes (HLMRGs) are fundamentally dysregulated in sepsis and have great predictive potential. Therefore, we attempted to build an HLMRG signature to predict the prognosis of patients with sepsis.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!