Redundant roles of EGFR ligands in the ERK activation waves during collective cell migration.

Autor:	Lin S; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Hirayama D; Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Maryu G; Division of Quantitative Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Japan., Matsuda K; Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Hino N; Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan., Deguchi E; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Aoki K; Division of Quantitative Biology, National Institute for Basic Biology, National Institutes of Natural Sciences, Okazaki, Japan.; Quantitative Biology Research Group, Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, Okazaki, Japan.; Department of Basic Biology, School of Life Science, SOKENDAI (The Graduate University for Advanced Studies), Okazaki, Japan., Iwamoto R; Research Institute for Microbial Diseases, Osaka University, Osaka, Japan., Terai K; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan., Matsuda M; Department of Pathology and Biology of Diseases, Graduate School of Medicine, Kyoto University, Kyoto, Japan matsuda.michiyuki.2c@kyoto-u.ac.jp.; Research Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.; Institute for Integrated Cell-Material Sciences, Kyoto University, Kyoto, Japan.
Jazyk:	angličtina
Zdroj:	Life science alliance [Life Sci Alliance] 2021 Oct 19; Vol. 5 (1). Date of Electronic Publication: 2021 Oct 19 (Print Publication: 2022).
DOI:	10.26508/lsa.202101206
Abstrakt:	Epidermal growth factor receptor (EGFR) plays a pivotal role in collective cell migration by mediating cell-to-cell propagation of extracellular signal-regulated kinase (ERK) activation. Here, we aimed to determine which EGFR ligands mediate the ERK activation waves. We found that epidermal growth factor ( EGF )-deficient cells exhibited lower basal ERK activity than the cells deficient in heparin-binding EGF ( HBEGF ), transforming growth factor alpha ( TGFα ) or epiregulin ( EREG ), but all cell lines deficient in a single EGFR ligand retained the ERK activation waves. Surprisingly, ERK activation waves were markedly suppressed, albeit incompletely, only when all four EGFR ligands were knocked out. Re-expression of the EGFR ligands revealed that all but HBEGF could restore the ERK activation waves. Aiming at complete elimination of the ERK activation waves, we further attempted to knockout NRG1 , a ligand for ErbB3 and ErbB4, and found that NRG1 -deficiency induced growth arrest in the absence of all four EGFR ligand genes. Collectively, these results showed that EGFR ligands exhibit remarkable redundancy in the propagation of ERK activation waves during collective cell migration. (© 2021 Lin et al.)
Databáze:	MEDLINE
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