{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:21:37Z","timestamp":1792783297958,"version":"4.5.0"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Balikesir University","id":[{"id":"https:\/\/ror.org\/02tv7db43","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cell Biochem Biophys"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The MMP14 gene, which encodes the only membrane-bound collagenase, is highly expressed in malignant tumors and plays a decisive role in invasiveness. This study investigated the transcriptional regulation of MMP14 by the TGF-\u03b2 cytokine and hypoxia in PC3 prostate carcinoma cells. Bioinformatic analysis confirmed the presence of key regulatory elements in the MMP14 promoter, specifically the HRE (for HIF-1\u03b1) and SMAD binding sites. Three 5\u2032 deletion fragments of the MMP14 promoter (P1: \u22121251\/+75; P2: \u2212649\/+75; P3: \u2212176\/+75) were cloned for functional analysis. PC3 cells were treated with TGF-\u03b2, the hypoxia-mimetic CoCl\n                    <jats:sub>2<\/jats:sub>\n                    , and the combination. Gene and protein expression were analyzed using Real-Time PCR and Immunofluorescence Cytochemistry (IFC), respectively, while promoter activities were assessed via a Luciferase reporter assay. COL1A expression was also evaluated to explore its association with MMP14-mediated extracellular matrix remodeling. Hypoxia emerged as the dominant inductive factor. MMP14 mRNA and protein levels were significantly elevated under hypoxic and combined TGF-\u03b2\/CoCl\n                    <jats:sub>2<\/jats:sub>\n                    conditions. Promoter analysis revealed that the full-length P1 construct was consistently upregulated by all treatments. However, the shorter P2 and P3 fragments exhibited a decrease in activity with TGF-\u03b2 alone, suggesting a complex, region-specific regulation predominantly influenced by hypoxic signaling. Critically, COL1A1 mRNA expression was observed in hypoxic groups with elevated MMP14 levels, indicating a possible inverse relationship between MMP14 induction and COL1A-associated extracellular matrix remodeling. Hypoxia is the primary driver of MMP14 induction and protein accumulation in PC3 cells, with TGF-\u03b2 acting as a complex co-regulator whose activating effect is potentiated under low-oxygen stress. These findings highlight the contribution of the HIF\/MMP14 axis to invasion-associated molecular regulation in prostate cancer.\n                  <\/jats:p>","DOI":"10.1007\/s12013-026-02102-3","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T10:21:04Z","timestamp":1782382864000},"page":"4025-4034","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Dual Role of TGF-\u03b2 and Hypoxia on MMP14-Mediated Invasion in PC3 Cells"],"prefix":"10.1007","volume":"84","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6758-8556","authenticated-orcid":false,"given":"Derya","family":"Okuyan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1711-7734","authenticated-orcid":false,"given":"Hanife","family":"Akta\u015f","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-6447","authenticated-orcid":false,"given":"Fatma","family":"Poyrazl\u0131","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1754-0700","authenticated-orcid":false,"given":"S\u00fcmeyye Aydo\u011fan","family":"T\u00fcrko\u011flu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"2102_CR1","doi-asserted-by":"crossref","unstructured":"Kaur, J., & Reinhardt, D. 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