XBP1s acts as a transcription factor of IRE1α and promotes proliferation of colon cancer cells

Liu, Shuting; Gao, Qiang; Li, Yuyao; Lun, Jie; Yu, Mengchao; Zhang, Hongwei; Fang, Jing

doi:10.1016/j.abb.2023.109552

Cited by 5 publications

(6 citation statements)

References 40 publications

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“…Numerous studies have pointed out that ERS is not only involved in the development of multiple tumors but can also affect chemoresistance, immune function and invasive metastasis of tumor cells 23–25 . In CRC, when ERS, IRE1α is activated to produce XBP1s by cutting mRNA, while XBP1s acts as a transcription factor binding to IRE1α promoter to transcribe IRE1 α to form an IRE1α‐XBP1s axis to induce cancer cell proliferation 26 . In the process of ERS‐induced epithelial‐mesenchymal transformation (EMT), GRP78/PERK signaling pathway is activated, which promotes nuclear translocation of ATF4 and increases the transcriptional activity of interleukin‐like met inducers, which accelerates tumor progression 27 .…”

Section: Discussionmentioning

confidence: 99%

“… 23 , 24 , 25 In CRC, when ERS, IRE1α is activated to produce XBP1s by cutting mRNA, while XBP1s acts as a transcription factor binding to IRE1α promoter to transcribe IRE1 α to form an IRE1α‐XBP1s axis to induce cancer cell proliferation. 26 In the process of ERS‐induced epithelial‐mesenchymal transformation (EMT), GRP78/PERK signaling pathway is activated, which promotes nuclear translocation of ATF4 and increases the transcriptional activity of interleukin‐like met inducers, which accelerates tumor progression. 27 In pancreatic cancer, activation of ERS induces the epithelial‐mesenchymal transition, which exacerbates tumor cell invasion and metastasis and contributes to accelerated tumor progression.…”

Section: Discussionmentioning

confidence: 99%

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Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options

Geng

Xie

et al. 2023

Cancer Medicine

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Background An increasing body of evidence supports an essential role for endoplasmic reticulum stress (ERS) in colorectal cancer (CRC). In this study, we developed an ERS‐related genes (ERSRGs) model to aid in the prognostic evaluation and treatment of CRC patients. Methods The training set and validation set data were extracted from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. ERSRGs were obtained from the GeneCards database. A prognostic risk scoring model was constructed using the least absolute shrinkage and selection operator (LASSO) along with univariate Cox regression analysis. To further predict the probability of survival for patients at 1, 2, and 3 years, a nomogram was devised. The advantages of the prognostic risk score model in screening patients’ sensitive to chemotherapy and immunotherapy were analyzed by drug sensitivity analysis and immune correlation analysis. Finally, hub genes associated with poor prognosis in the risk model were screened by Protein–protein interaction (PPI) network and their expression was validated using clinical specimens. Results A risk model for overall survival (OS) was developed using 16 ERSRGs associated with prognosis. Through analyses, we demonstrated a high degree of reliability for the prognostic risk scoring model. The constructed nomograms performed well in predicting patient survival over 1, 3, and 5 years. The calibration curve and decision curve analysis (DCA) supported a high degree of accuracy for the model. Patients in the low‐risk group had a lower IC50 for the common chemotherapy drug, 5‐FU, and responded better to immunotherapy. hub poor prognostic genes were validated in CRC clinical specimens. Conclusion We have identified and validated a new ERS prognostic marker that can accurately predict the survival status of CRC patients for clinicians and better provide personalized treatment plans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options

Geng

Xie

et al. 2023

Cancer Medicine

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“…These facts clearly demonstrate that neoplastic cells can acquire the ability to self-select, allowing them to survive in unfavourable environments [35][36]. The positive modulation of IRE1α induces the expression of XBP1, XBP1s and ERAD, further facilitating the survival of the malignant cell [21,37]. PERK activation via ARE, Keap1 and ATF4 may also favour the survival of neoplastic cells in hostile environments with nutrient deficiency, ATP shortage, ROS production and hypoxia [4,38].…”

Section: Antagonistic Mechanisms Observed By Upr Activation By the Erementioning

confidence: 95%

“…Yet, XBP1 is a biomarker of CRC invasion and metastasis, and its expression accelerates cancer cell invasion, suppressed by knockout of XBP1 using small interfering RNA (siRNA). When XBP1s is silenced, VEGF receptor 2 (VEGF-R2) levels, recognized as inducers of tumour angiogenesis, are drastically reduced [37,51]. XBP1s inhibits the expression of the tumour suppressor TAp73, a member of the p53 protein family, by binding directly to the TAp73 promoter and suppressing its transcriptional activity.…”

Section: Ire1α As a Protagonist In The Angiogenesis Of Crc Developmentmentioning

confidence: 99%

“…Solid tumours initially develop in the absence of vascularization, but as they grow they are exposed to various growth-restrictive conditions, such as ischemia, hypoxia and nutrient (glucose) deprivation. IRE1α activation is a common determinant that triggers hypoxia and hypoglycaemia-dependent signaling pathways leading to VEGF-A over-expression [37]. An experiment using an animal model lacking IRE1α failed to increase VEGF-A expression under conditions of hypoxia and hypoglycaemia, thus proving that IRE1α-dependent signaling pathways play an indispensable role in response to ischemia, indicating that IRE1α as a potentially useful therapeutic target to reduce angiogenesis and tumour growth [54].…”

Section: Ire1α As a Protagonist In The Angiogenesis Of Crc Developmentmentioning

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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Morin suppresses mTORc1/IRE-1α/JNK and IP3R-VDAC-1 pathways: Crucial mechanisms in apoptosis and mitophagy inhibition in experimental Huntington's disease, supported by in silico molecular docking simulations

El-Emam,

Sheta,

El-Abhar

et al. 2024

Life Sciences

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XBP1s acts as a transcription factor of IRE1α and promotes proliferation of colon cancer cells

Cited by 5 publications

References 40 publications

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options

Characteristics of endoplasmic reticulum stress in colorectal cancer for predicting prognosis and developing treatment options

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

Morin suppresses mTORc1/IRE-1α/JNK and IP3R-VDAC-1 pathways: Crucial mechanisms in apoptosis and mitophagy inhibition in experimental Huntington's disease, supported by in silico molecular docking simulations

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