Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer

Byeon, Sun-Ju; Lee, Hye Seung; Kim, Min Ah; Lee, Byung Lan; Kim, Woo Ho

doi:10.1159/000464250

Cited by 11 publications

(9 citation statements)

References 30 publications

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“…Another important molecule for EGFR signaling with an prognostic impact is its ligand AREG (39). Overexpression of AREG has been linked to therapeutic resistance (40).…”

Section: Discussionmentioning

confidence: 99%

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma

Kansy¹,

Aderhold

Huber

et al. 2020

Cancer Genomics Proteomics

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Background: We investigated the expression patterns of cluster of differentiation (CD) 44 and amphiregulin (AREG), two signaling molecules essential for cell proliferation and differentiation, under the influence of selective tyrosine kinase inhibitors (TKIs) in human papillomavirus (HPV) + and HPV − squamous carcinoma cell lines. Materials and Methods: The protein expression of CD44 and AREG was determined by sandwich enzymelinked immunosorbent assay in HPV − cell lines UMSCC-11A and UMSCC-14C, and HPV + CERV-196 cells after TKI treatment. Results: The expression of AREG and CD44 was dependent on the cell line's HPV status. AREG expression increased after incubation with nilotinib in HPV + tumor cells. The expression of CD44 was significantly influenced by all drugs; its expression under selective epidermal growth factor receptor inhibition was mostly reduced, whereas nilotinib led to an exceptional increase of CD44 expression. Conclusion: The selective drug treatment options significantly influenced the expression of CD44 and AREG in HPV − and HPV + tumor cells, constituting the need for personalized treatment options.

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“…Another important molecule for EGFR signaling with an prognostic impact is its ligand AREG (39). Overexpression of AREG has been linked to therapeutic resistance (40).…”

Section: Discussionmentioning

confidence: 99%

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma

Kansy¹,

Aderhold

Huber

et al. 2020

Cancer Genomics Proteomics

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“…However, the clinicopathologic implications of other ligands, including HBEGF, TGF, betacellulin, and EGF, are insufficiently investigated. For HBEGF, a pivotal role in cancer progression has been proposed in various cancers, including cervical, breast, and gastric cancers [ 20 - 23 ]. In CRC, Kawasaki et al [ 24 ] suggested that HBEGF has roles in CRC progression through the recruitment of intestinal myofibroblasts.…”

Section: Discussionmentioning

confidence: 99%

Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer

et al. 2018

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PurposeMolecular treatments targeting epidermal growth factor receptors (EGFRs) are important strategies for advanced colorectal cancer (CRC). However, clinicopathologic implications of EGFRs and EGFR ligand signaling have not been fully evaluated. We evaluated the expression of EGFR ligands and correlation with their receptors, clinicopathologic factors, and patients’ survival with CRC.Materials and MethodsThe expression of EGFR ligands, including heparin binding epidermal growth factor-like growth factor (HBEGF), transforming growth factor (TGF), betacellulin, and epidermal growth factor (EGF), were evaluated in 331 consecutive CRC samples using mRNA in situ hybridization (ISH). We also evaluated the expression status of EGFR, human epidermal growth factor receptor 2 (HER2), HER3, and HER4 using immunohistochemistry and/or silver ISH.ResultsUnlike low incidences of TGF (38.1%), betacellulin (7.9%), and EGF (2.1%), HBEGF expression was noted in 62.2% of CRC samples. However, the expression of each EGFR ligand did not reveal significant correlations with survival. The combined analyses of EGFR ligands and EGFR expression indicated that the ligands‒/EGFR+ group showed a significant association with the worst disease-free survival (DFS; p=0.018) and overall survival (OS; p=0.005). It was also an independent, unfavorable prognostic factor for DFS (p=0.026) and OS (p=0.007). Additionally, HER4 nuclear expression, regardless of ligand expression, was an independent, favorable prognostic factor for DFS (p=0.034) and OS (p=0.049), by multivariate analysis.ConclusionLigand-independent EGFR overexpression was suggested to have a significant prognostic impact; thus, the expression status of EGFR ligands, in addition to EGFR, might be necessary for predicting patients' outcome in CRC.

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“…HB-EGF might promote tumor growth and EMT by IL-4-conditioned media from macrophages [282]. Besides HB-EGF, other ErbB ligands (transforming growth factor-α (TGF-α) and amphiregulin (AREG)) have a prognostic impact on gastric cancer and might make up potential targets in cancer therapy [283][284][285]. Furthermore, trastuzumab sensitivity in gastric cancer can be predicted by HB-EGF expression [286].…”

Section: Heparin-binding Epidermal Growth Factor and Matrix Metalloprmentioning

confidence: 99%

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

Baj

Korona-Głowniak

Forma

et al. 2020

Cells

119

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Helicobacter pylori (H. pylori) is one of the most common human pathogens, affecting half of the world's population. Approximately 20% of the infected patients develop gastric ulcers or neoplastic changes in the gastric stroma. An infection also leads to the progression of epithelial-mesenchymal transition within gastric tissue, increasing the probability of gastric cancer development. This paper aims to review the role of H. pylori and its virulence factors in epithelial-mesenchymal transition associated with malignant transformation within the gastric stroma. The reviewed factors included: CagA (cytotoxin-associated gene A) along with induction of cancer stem-cell properties and interaction with YAP (Yes-associated protein pathway), tumor necrosis factor α-inducing protein, Lpp20 lipoprotein, Afadin protein, penicillin-binding protein 1A, microRNA-29a-3p, programmed cell death protein 4, lysosomal-associated protein transmembrane 4β, cancer-associated fibroblasts, heparin-binding epidermal growth factor (HB-EGF), matrix metalloproteinase-7 (MMP-7), and cancer stem cells (CSCs). The review summarizes the most recent findings, providing insight into potential molecular targets and new treatment strategies for gastric cancer.

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Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer

Cited by 11 publications

References 30 publications

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma

Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

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Expression of the ERBB Family of Ligands and Receptors in Gastric Cancer

Cited by 11 publications

References 30 publications

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV+ and HPV− Squamous Cell Carcinoma

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV+ and HPV− Squamous Cell Carcinoma

Ligand-Independent Epidermal Growth Factor Receptor Overexpression Correlates with Poor Prognosis in Colorectal Cancer

Mechanisms of the Epithelial–Mesenchymal Transition and Tumor Microenvironment in Helicobacter pylori-Induced Gastric Cancer

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Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma

Expression Patterns of CD44 and AREG Under Treatment With Selective Tyrosine Kinase Inhibitors in HPV⁺ and HPV⁻ Squamous Cell Carcinoma