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Review

Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research

1
Department of Cell and Molecular Biology, Cancer Center and Research Institute, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA
2
School of Medicine, Deakin University, Locked Bag 20000, Geelong, VIC 3220, Australia
*
Author to whom correspondence should be addressed.
Academic Editor: Natascia Tiso
Cells 2021, 10(5), 1132; https://doi.org/10.3390/cells10051132
Received: 30 March 2021 / Revised: 29 April 2021 / Accepted: 3 May 2021 / Published: 7 May 2021
(This article belongs to the Special Issue Signaling Pathway Analysis and Disease Modeling in Zebrafish)
Studies conducted in several fish species, e.g., Xiphophorus hellerii (green swordtail) and Xiphophorus maculatus (southern platyfish) crosses, Oryzias latipes (medaka), and Danio rerio (zebrafish), have identified an oncogenic role for the receptor tyrosine kinase, Xmrk, a gene product closely related to the human epidermal growth factor receptor (EGFR), which is associated with a wide variety of pathological conditions, including cancer. Comparative analyses of Xmrk and EGFR signal transduction in melanoma have shown that both utilize STAT5 signaling to regulate apoptosis and cell proliferation, PI3K to modulate apoptosis, FAK to control migration, and the Ras/Raf/MEK/MAPK pathway to regulate cell survival, proliferation, and differentiation. Further, Xmrk and EGFR may also modulate similar chemokine, extracellular matrix, oxidative stress, and microRNA signaling pathways in melanoma. In hepatocellular carcinoma (HCC), Xmrk and EGFR signaling utilize STAT5 to regulate cell proliferation, and Xmrk may signal through PI3K and FasR to modulate apoptosis. At the same time, both activate the Ras/Raf/MEK/MAPK pathway to regulate cell proliferation and E-cadherin signaling. Xmrk models of melanoma have shown that inhibitors of PI3K and MEK have an anti-cancer effect, and in HCC, that the steroidal drug, adrenosterone, can prevent metastasis and recover E-cadherin expression, suggesting that fish Xmrk models can exploit similarities with EGFR signal transduction to identify and study new chemotherapeutic drugs. View Full-Text
Keywords: epidermal growth factor receptor; Xmrk; cancer; zebrafish; Xiphophorus; signal transduction; drug discovery; melanoma epidermal growth factor receptor; Xmrk; cancer; zebrafish; Xiphophorus; signal transduction; drug discovery; melanoma
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MDPI and ACS Style

Monroe, J.D.; Basheer, F.; Gibert, Y. Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research. Cells 2021, 10, 1132. https://doi.org/10.3390/cells10051132

AMA Style

Monroe JD, Basheer F, Gibert Y. Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research. Cells. 2021; 10(5):1132. https://doi.org/10.3390/cells10051132

Chicago/Turabian Style

Monroe, Jerry D., Faiza Basheer, and Yann Gibert. 2021. "Xmrks the Spot: Fish Models for Investigating Epidermal Growth Factor Receptor Signaling in Cancer Research" Cells 10, no. 5: 1132. https://doi.org/10.3390/cells10051132

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