Reference - Detail
| RRC ID | 82023 |
|---|---|
| Author | Deguchi E, Lin S, Hirayama D, Matsuda K, Tanave A, Sumiyama K, Tsukiji S, Otani T, Furuse M, Sorkin A, Matsuda M, Terai K. |
| Title | Low-affinity ligands of the epidermal growth factor receptor are long-range signal transmitters in collective cell migration of epithelial cells. |
| Journal | Cell Rep |
| Abstract |
Canonical epidermal growth factor (EGF) receptor (EGFR) activation involves the binding of seven EGFR ligands (EGFRLs); however, their extracellular dynamics remain elusive. Here, employing fluorescent probes and a tool for triggering ectodomain shedding, we show that epiregulin (EREG), a low-affinity EGFRL, rapidly and efficiently activates EGFR in Madin-Darby canine kidney (MDCK) epithelial cells and mouse epidermis. During collective cell migration, EGFR and extracellular signal-regulated kinase (ERK) activation waves propagate in an a disintegrin and metalloprotease 17 (ADAM17) sheddase- and EGFRL-dependent manner. Upon induced EGFRL shedding, low-affinity ligands EREG and amphiregulin (AREG) mediate faster and broader ERK waves than high-affinity ligands. Tight/adherens junction integrity is essential for ERK activation propagation, suggesting that tight intercellular spaces prefer the low-affinity EGFRLs for efficient signal transmission. In EREG-deficient mice, ERK wave propagation and cell migration were impaired during skin wound repair. We additionally show that heparin-binding EGF-like growth factor (HBEGF) primarily promotes surrounding cell motility. Our findings underscore the pivotal role of low-affinity EGFRLs in rapid intercellular signal transmission. |
| Volume | 43(11) |
| Pages | 114986 |
| Published | 2024-11-14 |
| DOI | 10.1016/j.celrep.2024.114986 |
| PII | S2211-1247(24)01337-8 |
| PMID | 39546398 |
| MeSH | ADAM17 Protein / metabolism Amphiregulin / metabolism Animals Cell Movement* Dogs Epidermis / metabolism Epiregulin* / metabolism Epithelial Cells* / metabolism ErbB Receptors* / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism Heparin-binding EGF-like Growth Factor / genetics Heparin-binding EGF-like Growth Factor / metabolism Humans Ligands Madin Darby Canine Kidney Cells Mice Signal Transduction Wound Healing |
| IF | 8.109 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 15 |
| Altmetric score changes over past 6months | 1.5 |
| Resource | |
| Human and Animal Cells | MDCK(RCB0995) |
| DNA material | pCMV-VSV-G-RSV-Rev (RDB04393) |