{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T11:28:39Z","timestamp":1786447719522,"version":"build-2736575974"},"reference-count":62,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Regional Development Funds","award":["002-24"],"award-info":[{"award-number":["002-24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Growth factors are molecules that interact with specific membrane receptors and induce cellular proliferation. In malignancy, this growth factor\u2013receptor interaction constitutes one of the \u201challmarks of cancer\u201d and may result in uncontrolled cell growth. Proadrenomedullin N-terminal 20 peptide (PAMP) derives from proadrenomedullin and acts as an angiogenic peptide, and recent studies suggest it may be a tumor growth factor. In addition, it has been suggested that CXCR7 may be PAMP\u2019s membrane receptor in particular cell types. Here, we combined advanced docking and molecular dynamic simulation studies to evaluate PAMP\u2019s binding to CXCR7. Then, we used two melanoma cell lines and checked whether PAMP influences their shape, proliferation, migration, and invasion capacities. The signal transduction activated by PAMP was tested by Western blotting, and receptor involvement was investigated with specific inhibitors. This study shows that PAMP binds to active site 1 of CXCR7. It also increases melanoma cell proliferation through an autocrine growth loop. In contrast, PAMP reduced migration and invasion of these cells in a dose-dependent manner. PAMP was also responsible for modifying the actin cytoskeleton of both cell lines, producing a more elongated morphology. In addition, the presence of PAMP elevated ERK and AKT phosphorylation and increased CXCR7 and \u03b2-arrestin expression. Furthermore, specific inhibitors confirmed that these effects are mediated by the CXCR7\/CXCR4\/\u03b2-arrestin axis. In summary, we have shown that PAMP acts as a growth factor for melanoma cells while reducing their migration and invasion potential. These effects seem to be mediated by the CXCR7\/CXCR4\/\u03b2-arrestin axis. Altogether, these results suggest that PAMP inhibitors may be used as antitumor agents in melanoma.<\/jats:p>","DOI":"10.3390\/molecules31162791","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T10:32:16Z","timestamp":1786444336000},"page":"2791","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Proadrenomedullin N-Terminal 20 Peptide (PAMP) Increases Proliferation and Induces Cytoskeleton Remodeling in Melanoma Cells Through the CXCR7\/CXCR4\/\u03b2-Arrestin Axis"],"prefix":"10.3390","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9613-1571","authenticated-orcid":false,"given":"Tom Kalathil","family":"Raju","sequence":"first","affiliation":[{"name":"Angiogenesis Group, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5960-8569","authenticated-orcid":false,"given":"Pablo","family":"Garrido","sequence":"additional","affiliation":[{"name":"Angiogenesis Group, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4391-5537","authenticated-orcid":false,"given":"Josune","family":"Garc\u00eda-Sanmart\u00edn","sequence":"additional","affiliation":[{"name":"Angiogenesis Group, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4882-4044","authenticated-orcid":false,"given":"Alfredo","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Angiogenesis Group, Center for Biomedical Research of La Rioja (CIBIR), 26006 Logro\u00f1o, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2254","DOI":"10.1016\/j.cell.2025.12.049","article-title":"Hallmarks of cancer-Then and now, and beyond","volume":"189","author":"Hanahan","year":"2026","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1177\/0300985809352981","article-title":"Growth factors as active participants in carcinogenesis: A perspective","volume":"47","author":"Halper","year":"2010","journal-title":"Vet. 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