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Here, we have studied the functional role of complement factor I (CFI) in the progression of cSCC. CFI was knocked down in cSCC cells, and RNA\u2010seq analysis was performed. Significant downregulation of genes in IPA biofunction categories <jats:italic>Proliferation of cells<\/jats:italic> and <jats:italic>Growth of malignant tumor<\/jats:italic>, in Gene Ontology (GO) terms <jats:italic>Metallopeptidase activity<\/jats:italic> and <jats:italic>Extracellular matrix component<\/jats:italic>, as well as Reactome <jats:italic>Degradation of extracellular matrix<\/jats:italic> was detected after CFI knockdown. Further analysis of the latter three networks, revealed downregulation of several genes coding for invasion\u2010associated matrix metalloproteinases (MMPs) after CFI knockdown. The downregulation of MMP\u201013 and MMP\u20102 was confirmed at mRNA, protein and tissue levels by qRT\u2010qPCR, Western blot and immunohistochemistry, respectively. Knockdown of CFI decreased the invasion of cSCC cells through type I collagen. Overexpression of CFI in cSCC cells resulted in enhanced production of MMP\u201013 and MMP\u20102 and increased invasion through type I collagen and Matrigel, and in increased ERK1\/2 activation and cell proliferation. Altogether, these findings identify a novel mechanism of action of CFI in upregulation of MMP\u201013 and MMP\u20102 expression and cSCC invasion. These results identify CFI as a prospective molecular marker for invasion and metastasis of cSCC.<\/jats:p>","DOI":"10.1111\/exd.14349","type":"journal-article","created":{"date-parts":[[2021,4,4]],"date-time":"2021-04-04T09:41:53Z","timestamp":1617529313000},"page":"1631-1641","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Complement factor I upregulates expression of matrix metalloproteinase\u201013 and \u20102 and promotes invasion of cutaneous squamous carcinoma cells"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0774-2675","authenticated-orcid":false,"given":"Pegah","family":"Rahmati Nezhad","sequence":"first","affiliation":[{"name":"Department of Dermatology University of Turku and Turku University Hospital  Turku Finland"},{"name":"FICAN West Cancer Centre Laboratory University of Turku and Turku University Hospital  Turku 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