{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,14]],"date-time":"2026-02-14T05:53:23Z","timestamp":1771048403005,"version":"3.50.1"},"reference-count":40,"publisher":"Scientific Scholar","content-domain":{"domain":["cytojournal.com"],"crossmark-restriction":true},"short-container-title":["Cytojournal"],"abstract":"\nObjective:<\/jats:title>\nHypoxia intensely drives the development of malignant tumors, including skin cutaneous melanoma (SKCM). S-phase kinase-interacting protein 2 (SKP2) is known to participate in the progression of human tumors. The purpose of this study is to explore whether SKP2 acts as a hypoxic response gene during SKCM progression.<\/jats:p>\n<\/jats:sec>\n\nMaterial and Methods:<\/jats:title>\nSKP2 expression in SKCM tissues was analyzed using The Cancer Genome Atlas database. Anoxic experiments were conducted to simulate an anoxic environment. 5-Ethynyl-2'-deoxyuridine and colony formation assays were used to evaluate SKCM cell growth. Scratch healing and Transwell assays were applied to measure the migration and invasion abilities of SKCM cells. An immunoblotting assay was used to detect the levels of extracellular signal-regulated kinase (ERK)1\/2 pathway proteins. In addition, the ERK-specific agonist LM22B-10 was added to confirm whether the ERK1\/2 signaling pathway is required for SKP2-mediated SKCM progression under hypoxic conditions.<\/jats:p>\n<\/jats:sec>\n\nResults:<\/jats:title>\nSKP2 was significantly upregulated in SKCM tissues and closely related to adverse outcomes in patients. Moreover, SKP2 levels increased in SKCM cells under normoxic conditions and further elevated under hypoxic conditions. SKP2 deficiency led to the reduced proliferation, migration, and invasion potential of cells under hypoxic conditions. Mechanically, SKP2 silencing blocked the ERK1\/2 pathway in hypoxic cells, and the activation of the ERK1\/2 pathway rescued the suppression effect of SKP2 on the hypoxia-induced progression of SKCM.<\/jats:p>\n<\/jats:sec>\n\nConclusion:<\/jats:title>\nSKP2 deficiency repressed the hypoxic-induced progression of SKCM through the ERK1\/2 pathway. This novel discovery regarding the SKP2\/ERK1\/2 axis might provide new insights into the pathogenesis of SKCM.<\/jats:p>\n<\/jats:sec>","DOI":"10.25259\/cytojournal_117_2024","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T06:35:36Z","timestamp":1737700536000},"page":"9","update-policy":"https:\/\/doi.org\/10.25259\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hypoxia-induced S-phase kinase-interacting protein 2 knockdown repressed the progression of melanoma through extracellular signal-regulated kinase 1\/2 pathway"],"prefix":"10.25259","volume":"22","author":[{"given":"Yong","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereal Diseases, Yihe Women\u2019s and Children\u2019s Hospital, Chaoyang District, Beijing, China,"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"10894","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"10.25259\/Cytojournal_117_2024\/ref-1","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1016\/S0140-6736(23)00821-8","article-title":"Cutaneous melanoma","volume":"402","author":"Long","year":"2023","journal-title":"Lancet"},{"key":"10.25259\/Cytojournal_117_2024\/ref-2","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"10.25259\/Cytojournal_117_2024\/ref-3","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.hoc.2020.08.010","article-title":"Biology of melanoma","volume":"35","author":"Ostrowski","year":"2021","journal-title":"Hematol Oncol Clin North Am"},{"key":"10.25259\/Cytojournal_117_2024\/ref-4","first-page":"81","article-title":"Chinese expert consensus on the surgical treatment of cutaneous\/acral melanoma V1.0","volume":"42","author":"Soft Tissue Tumor and Melanoma Group of Sarcoma Committee. 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