ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway

Wen, Xin; Chen, Si; Qiu, Hui; Wang, Wei; Zhang, Nie; Liu, Wanming; Wang, Tingting; Ding, Xin; Zhang, Longzhen

doi:10.3389/fonc.2022.887068

Cited by 10 publications

(3 citation statements)

References 50 publications

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“…Previous studies showed that ITGB5 contributes to the resistance to radio-and chemotherapy [38] and also affect EMT and tumor growth in carcinoma cells [39]. Its overexpression is associated with the activation of survival signaling cascades [40], enhanced adhesion and motility [41], preserved stem cell-like traits [42], suppressed anti-tumor immunity [43], and stimulated angiogenesis [42]. These mechanisms collectively suggest mitigation of apoptosis, promotion of invasion and metastasis, conservation of drug-resistant subpopulations, suppression of immunologic cytotoxicity, reduction of intracellular chemotherapy concentrations, and enhancement of vascularization, thus countering TDM-1 treatment.…”

Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways Governing T-DM1 Resistance in OE-19 Esophageal Cancer Cells through Bioinformatics Analysis

Yazdani,

Mottaghi-Dastjerdi,

Ghorbani

et al. 2023

Preprint

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Introduction : Esophageal Cancer (EC) ranks among the most common malignancies worldwide. Most EC patients acquire drug resistance to chemotherapy either intrinsically or acquired after T-DM1 treatment, which shows that increasing or decreasing the expression of particular genes might influence chemotherapeutic sensitivity or resistance. Therefore, gaining a deeper understanding of the altered expression of genes involved in EC drug resistance and developing new therapeutic methods are essential targets for continued advancement in EC therapy. Methods The present study aimed to find critical regulatory genes/pathways in the progression of T-DM1 resistance in OE-19 EC cells. Expression datasets were extracted from GEO omnibus. Gene interactions were analyzed, and the protein-protein interaction network was drawn. Then, enrichment analysis of the hub genes and network cluster analysis of the hub genes was performed. Finally, the genes were screened in the DrugBank database as therapeutic targets. Results In the current study nine hub genes were identified in TDM-1 resistant EC cells (CTGF, CDH17, THBS1, CXCL8, NRP1, ITGB5, EDN1, FAT1, and PTGS2). the KEGG analysis highlighted the IL-17 signaling pathway and ECM-receptor interaction pathway as the most important pathways; cluster analysis also showed the significance of these pathways; therefore, the genes involved in these two pathways, including CXCL8, FSCN1, PTGS2, SERPINE2, LEF1, THBS1, CCN2, TAGLN, CDH11, ITGA6 were searched in DrugBank as therapeutic targets. The DrugBank analysis suggests a potential role for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in reducing T-DM1 drug resistance in EC. Conclusion This comprehensive bioinformatics analysis deeply explains the molecular mechanisms governing TDM-1 resistance in EC. The identified hub genes and their associated pathways offer potential targets for therapeutic interventions. Moreover, the potential role of NSAIDs in mitigating T-DM1 resistance presents an intriguing avenue for further investigation. This research contributes significantly to the field and establishes a basis for further research to enhance treatment efficacy for EC patients.

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Section: Discussionmentioning

confidence: 99%

Identification of Key Genes and Pathways Governing T-DM1 Resistance in OE-19 Esophageal Cancer Cells through Bioinformatics Analysis

Yazdani,

Mottaghi-Dastjerdi,

Ghorbani

et al. 2023

Preprint

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“…Metabolic reprogramming also contributes to radiation resistance in PDAC. Overexpression of Mucin1 (Muc1) in PDAC cells can mitigate radiationinduced cytotoxicity by enhancing glycolysis, the pentose phosphate pathway, and nucleotide biosynthesis [24][25][26][27].…”

Section: Reversing Radiation Resistance Naturementioning

confidence: 99%

Making incurable pancreatic cancer curable

An,

Xie,

Xie

2023

Malignancy Spectrum

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Pancreatic cancer is one of the deadliest malignancies, with limited effectiveness of standard therapies, resulting in little improvement in the 5‐year survival rate over the past few decades. However, advanced radiotherapy techniques and emerging treatment modalities, such as immunotherapy and targeted therapy, are showing tremendous potential as effective treatment options for pancreatic cancer patients who were previously considered incurable. This review summarizes the current advances and challenges in pancreatic cancer treatment strategies and proposes further optimization directions, aiming to provide insights into the cure of incurable pancreatic cancer.

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“…The various phospho-proteins in this pathway are activated under assorted stressors, such as UV or ionizing radiation exposure, and play a role in the transcription of genes defining cell fate. For example, the MEK/ERK pathway has been shown to contribute to an anti-apoptotic pathway following radiation, providing cells with radioresistance [6,7]. ERK activation has been shown to trigger cell proliferation and to provide a survival advantage [8,9], although it has also been known to promote cell death under other conditions, depending upon its location and the extent of activation [10].…”

Section: Introductionmentioning

confidence: 99%

Modeling Radiation-Induced Epithelial Cell Injury in Murine Three-Dimensional Esophageal Organoids

Carswell,

Sridharan,

Chien

et al. 2024

Biomolecules

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Esophageal squamous cell carcinoma (ESCC) is a deadly consequence of radiation exposure to the esophagus. ESCC arises from esophageal epithelial cells that undergo malignant transformation and features a perturbed squamous cell differentiation program. Understanding the dose- and radiation quality-dependence of the esophageal epithelium response to radiation may provide insights into the ability of radiation to promote ESCC. We have explored factors that may play a role in esophageal epithelial radiosensitivity and their potential relationship to ESCC risk. We have utilized a murine three-dimensional (3D) organoid model that recapitulates the morphology and functions of the stratified squamous epithelium of the esophagus to study persistent dose- and radiation quality-dependent changes. Interestingly, although high-linear energy transfer (LET) Fe ion exposure induced a more intense and persistent alteration of squamous differentiation and 53BP1 DNA damage foci levels as compared to Cs, the MAPK/SAPK stress pathway signaling showed similar altered levels for most phospho-proteins with both radiation qualities. In addition, the lower dose of high-LET exposure also revealed nearly the same degree of morphological changes, even though only ~36% of the cells were predicted to be hit at the lower 0.1 Gy dose, suggesting that a bystander effect may be induced. Although p38 and ERK/MAPK revealed the highest levels following high-LET exposure, the findings reveal that even a low dose (0.1 Gy) of both radiation qualities can elicit a persistent stress signaling response that may critically impact the differentiation gradient of the esophageal epithelium, providing novel insights into the pathogenesis of radiation-induced esophageal injury and early stage esophageal carcinogenesis.

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ITGB5 promotes innate radiation resistance in pancreatic adenocarcinoma by promoting DNA damage repair and the MEK/ERK signaling pathway

Cited by 10 publications

References 50 publications

Identification of Key Genes and Pathways Governing T-DM1 Resistance in OE-19 Esophageal Cancer Cells through Bioinformatics Analysis

Identification of Key Genes and Pathways Governing T-DM1 Resistance in OE-19 Esophageal Cancer Cells through Bioinformatics Analysis

Making incurable pancreatic cancer curable

Modeling Radiation-Induced Epithelial Cell Injury in Murine Three-Dimensional Esophageal Organoids

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