What Are the Real Roles of Different ErbB Proteins in Barrett’s Esophagus

Chiba, Tsutomu

doi:10.1159/000080927

Cited by 3 publications

(3 citation statements)

References 16 publications

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“…ERBB family members including ERBB1/EGFR and ERBB2/HER2, are receptor tyrosine kinases that are often aberrantly activated leading to cancer cell migration, EMT, antitumor immunity and cancer cell survival [ 84 , 85 ]. Upregulation of both ERBB1/EGFR and ERBB2/HER2 is observed in progression from BE to EAC and increased surface expression has been used for in vivo detection using fluorescent peptides targeting these two proteins [ 86 , 87 , 88 , 89 , 90 ].…”

Section: Discussionmentioning

confidence: 99%

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

et al. 2022

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Esophageal adenocarcinoma (EAC) is a cancer characterized by rapidly rising incidence and poor survival, resulting in the need for new prevention and treatment options. We utilized two cranberry polyphenol extracts, one pro-anthocyanidin enriched (C-PAC) and a combination of anthocyanins, flavonoids, and glycosides (AFG) to assess inhibitory mechanisms utilizing premalignant Barrett’s esophagus (BE) and EAC derived cell lines. We employed reverse phase protein arrays (RPPA) and Western blots to examine cancer-associated pathways and specific signaling cascades modulated by C-PAC or AFG. Viability results show that C-PAC is more potent than AFG at inducing cell death in BE and EAC cell lines. Based on the RPPA results, C-PAC significantly modulated 37 and 69 proteins in JH-EsoAd1 (JHAD1) and OE19 EAC cells, respectively. AFG treatment significantly altered 49 proteins in both JHAD1 and OE19 cells. Bioinformatic analysis of RPPA results revealed many previously unidentified pathways as modulated by cranberry polyphenols including NOTCH signaling, immune response, and epithelial to mesenchymal transition. Collectively, these results provide new insight regarding mechanisms by which cranberry polyphenols exert cancer inhibitory effects targeting EAC, with implications for potential use of cranberry constituents as cancer preventive agents.

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Section: Discussionmentioning

confidence: 99%

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

et al. 2022

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“…There is an additional layer of complexity to this model when applying it to other cell lines, which express the ErbB RTKs at different levels. Reports in the literature have been inconsistent regarding how BTC induces ErbB3 phosphorylation (Riese et al, 1995;Pinkas-Kramarski et al, 1996;Riese et al, 1996;Chiba, 2004;Steinkamp et al, 2014). We postulate that the absolute and relative amounts of EGFR and ErbB3 in different cell lines are a potential source for these discrepancies.…”

Section: Discussionmentioning

confidence: 72%

Betacellulin (BTC) Biases the EGFR To Dimerize with ErbB3

2018

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There are 13 known endogenous ligands for the epidermal growth factor receptor (EGFR) and its closely related ErbB receptor family members. We previously reported that betacellulin (BTC) is more efficacious than epidermal growth factor (EGF) in mediating corneal wound healing, although the molecular basis for this difference was unknown. For the most part, differences between ligands can be attributed to variability in binding properties, such as the unique rate of association and dissociation, pH sensitivity, and selective binding to individual ErbB family members of each ligand. However, this was not the case for BTC. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that the response of BTC is not due to enhanced affinity or kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR-ErbB3 heterodimers when compared with EGF treatment. We observed that EGFR-ErbB3 heterodimers contribute to cell migration, because the addition of an ErbB3 antagonist (MM-121) or RNA interferencemediated knockdown of ErbB3 attenuates BTC-stimulated cell migration compared with EGF. Thus, we demonstrate that, despite both ligands binding to the EGFR, BTC biases the EGFR to dimerize with ErbB3 to regulate the biologic response.

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“…ErbB3 phosphorylation [118,[129][130][131][132]. We postulate that the variability in the absolute and relative amounts of EGFR and ErbB3 are a potential source for these discrepancies.…”

Section: Reports In the Literature Have Been Inconsistent Regarding Hmentioning

confidence: 99%

Epidermal growth factor-like ligands regulate dimer selection.

Rush¹

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Brian P. Ceresa, for guiding me through life as a scientist, and helping me to be the best independent researcher I can be. I especially am grateful that he reminds me that there is no failure, just lessons learned. As scientist, we learn often. I would like to thank my committee members, Dr. Bates and Dr. Hood, for their guidance and perspective on my research. Every researcher that has passed through the doors of the Ceresa lab was influential in my past, and influences my present and my future. I am grateful for the lessons learned and the friendships made along the way. However, I am most thankful for my first lab friend and collaborator, Dr. Peterson. We grew as scientist together, and I owe much of my success to her support, guidance and ability to help me laugh through the tough spots. Thanks to everyone in my lab network, without all of your help, shared supplies and shared knowledge I could not make science happen. Finally, without the support of my family, I would have never started, let alone finished anything. My father is, and will always be my favorite chemistry teacher, thanks Mr. Hall. Thanks to my late mother for her dedication to my success, you were always there for my three sisters and myself, and we are all better people because of you. Lastly, thanks to my husband, Brandon, for loving me, laughing with me and laughing at me when you absolutely should. The winding road of life is more interesting and fun doing it side-by-side with you.

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What Are the Real Roles of Different ErbB Proteins in Barrett’s Esophagus

Cited by 3 publications

References 16 publications

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

Cranberry Polyphenols in Esophageal Cancer Inhibition: New Insights

Betacellulin (BTC) Biases the EGFR To Dimerize with ErbB3

Epidermal growth factor-like ligands regulate dimer selection.

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