Nrf2/Keap1-Pathway Activation and Reduced Susceptibility to Chemotherapy Treatment by Acidification in Esophageal Adenocarcinoma Cells

Storz, Lucie; Walther, P.; Chemnitzer, Olga; Lyros, Orestis; Niebisch, Stefan; Jansen-Winkeln, Boris; Moulla, Yusef; Büch, Thomas; Gockel, Ines; Thieme, René

doi:10.3390/cancers13112806

Cited by 6 publications

(1 citation statement)

References 45 publications

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“…2 As one of the main risk factors of BE, chronic gastroesophageal reflux disease (GERD) causes the abnormal reflux of acid and bile salts into the esophagus, which can regulate oncogenic signaling pathways to promote the progression of BE and EAC. [3][4][5] Nevertheless, the detailed underlying mechanism is still elusive.…”

Section: Introductionmentioning

confidence: 99%

Exosome-Delivered EGFR Induced by Acidic Bile Salts Regulates Macrophage M2 Polarization to Promote Esophageal Adenocarcinoma Cell Proliferation

Chen,

Ding,

et al. 2024

OTT

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Purpose Chronic gastroesophageal reflux disease (GERD) causes the abnormal reflux of acid and bile salts, which would induce Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC). EGFR, as one of main components of the exosome, plays an important role in cancer progression. Here, we investigated the role of acidic bile salts (ABS)-induced exosomal EGFR in EAC cell proliferation. Methods Electronic microscopic examination and Western blot were used to identify exosomes. Western blot, siRNA transfection, enzyme-linked immunosorbent assay, qRT-PCR, cell viability detection, mouse xenograft tumor models, and immunohistochemical staining were performed to study the function of ABS-induced exosomal EGFR in cell proliferation. Results We found that ABS improved the exosomal EGFR level of normal human esophageal epithelial cells, BE cells, and BE-associated adenocarcinoma cells. The results were confirmed in the serum-derived exosomes from healthy persons and patients suffering from GERD, BE with or without GERD, and EAC with or without GERD. Moreover, cell line-derived exosomal EGFR was found to promote macrophage M2 polarization through the PI3K-AKT pathway. The co-incubation medium of macrophages and exosomes improved cell proliferation and tumor growth, which depended on the exosomal EGFR level. CCL18 was identified as the most effective component of the co-incubation medium to promote EAC cell proliferation by binding to its receptor PITPNM3 in vitro and in vivo. Conclusion Our findings demonstrate that ABS-induced exosomal EGFR regulates macrophage M2 polarization to promote EAC proliferation. This study provides an important insight into the role of ABS in EAC development.

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Section: Introductionmentioning

confidence: 99%

Exosome-Delivered EGFR Induced by Acidic Bile Salts Regulates Macrophage M2 Polarization to Promote Esophageal Adenocarcinoma Cell Proliferation

Chen,

Ding,

et al. 2024

OTT

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Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank

Yang,

Cheng,

Plum

et al. 2024

J Cancer Res Clin Oncol

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Purpose This study explored the association between triglyceride-glucose (TyG), TyG index with body mass index (TyG-BMI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C), metabolic score for insulin resistance (IR) (METS-IR) and the risk of esophageal cancer. Methods A total of 388,900 participants from the United Kingdom Biobank from 2006 to 2010 were included. Fine-Gray models, restricted cubic spline (RCS), and receiver operating characteristic (ROC) curves were used to assess the association between the four IR surrogates and the risk of esophageal cancer, specifically, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC). Results Ten years after recruitment, 0.16% (95%CI 0.11–0.26%) had esophageal cancer and 4.17% (95%CI 3.86–4.46%) are deceased. For each standard deviation increase in the TyG index, TyG-BMI, TG/HDL-C, and METS-IR, the risk of EAC increased by Hazard ratios (HR)1.16, 1.37, 1.08, and 1.36, respectively (all P < 0.05), while the risk of ESCC decreased by HRs 0.80, 0.67, 0.77, and 0.65, respectively. RCS analysis indicated that most relationships were nonlinear (P < 0.05). ROC curves showed that METS-IR had a more robust diagnostic efficacy than TyG, TyG-BMI, and TG/HDL-C. Conclusion TyG index, TyG-BMI, TG/HDL-C, and METS-IR were closely associated with the risk of EAC and ESCC. Additionally, METS-IR surpassed the other three IR indices in predicting and diagnosing the risks of EAC and ESCC. The METS-IR is expected to become a more effective metric for identifying populations at early risk of esophageal cancer and for improving risk stratification.

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Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma

et al. 2022

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Nrf2/Keap1-Pathway Activation and Reduced Susceptibility to Chemotherapy Treatment by Acidification in Esophageal Adenocarcinoma Cells

Cited by 6 publications

References 45 publications

Exosome-Delivered EGFR Induced by Acidic Bile Salts Regulates Macrophage M2 Polarization to Promote Esophageal Adenocarcinoma Cell Proliferation

Exosome-Delivered EGFR Induced by Acidic Bile Salts Regulates Macrophage M2 Polarization to Promote Esophageal Adenocarcinoma Cell Proliferation

Association between four insulin resistance surrogates and the risk of esophageal cancer: a prospective cohort study using the UK Biobank

Signaling pathways and their potential therapeutic utility in esophageal squamous cell carcinoma

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