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This study investigated the potential of A11, an Annexin A1 (ANXA1)\u2010derived peptide, to enhance VEM efficacy in both VEM\u2010sensitive and VEM\u2010resistant melanoma cells. We evaluated the effects of A11 in melanoma through in\u00a0vitro assays (including MTT, clonogenic survival, apoptosis, and cell cycle analysis) and in\u00a0vivo xenograft models in nude mice. Furthermore, we mechanistically interrogated A11\u2010mediated suppression of EphA2 expression and the downstream pS897\u2010EphA2\/AKT\/ERK signalling pathway in resistant and parental cell lines via Western blotting and immunohistochemistry (IHC). Critically, our study demonstrates that A11 inhibits melanoma cell proliferation and reverses VEM resistance through EphA2 downregulation, consequently ablating this oncogenic pathway. This research highlights the promising application value of A11 in improving the efficacy of VEM treatment in melanoma, particularly in VEM\u2010resistant melanoma.<\/jats:p>","DOI":"10.1111\/jcmm.71310","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T04:33:12Z","timestamp":1787200392000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ANXA1<\/scp>\n                    \u2010Derived Peptide Increases Melanoma Cell Sensitivity to Vemurafenib by Downregulating\n                    <scp>EphA2<\/scp>"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1615-5084","authenticated-orcid":false,"given":"Juan","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Pathology, the Second Xiangya Hospital Central South University  Changsha Hunan China"},{"name":"Department of Oncology, Xiangya Hospital Central South University  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