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We examined the expression and intracellular localization of MMP2\/9 in ZL55 malignant mesothelioma cells, as well as their regulation by ADP. Using real\u2010time PCR, we showed that activation of the P2Y1 receptor by ADP increased the expression of MMP2\/9 mRNAs; MMP2\/9 collected from conditioned media also showed an increase in activity; and ADP induced the nuclear localization of MMP2\/9. The effects of ADP on transcription of the MMPs were due to activation of c\u2010Src, Akt, and NF\u2010\u03baB, while ERK1\/2 phosphorylation was needed for the increase in enzymatic activity and the regulation of nuclear import. We also showed that the nuclear localization of MMP2\/9 induced by ADP causes the cleavage and inactivation of poly\u2010ADP\u2010ribose polymerase\u20101. These findings may help to elucidate the mechanisms regulating MMP2\/9 activation in ZL55 human epithelioid mesothelioma cells, and perhaps other cells. Therapeutic approaches that promote ADP accumulation in a tumor environment may constitute an effective means to induce anticancer activity.<\/jats:p>","DOI":"10.1111\/nyas.13922","type":"journal-article","created":{"date-parts":[[2018,7,9]],"date-time":"2018-07-09T04:40:00Z","timestamp":1531111200000},"page":"72-84","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Adenosine diphosphate regulates MMP2 and MMP9 activity in malignant mesothelioma cells"],"prefix":"10.1111","volume":"1431","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-9929","authenticated-orcid":false,"given":"Antonella","family":"Muscella","sequence":"first","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.) University of Salento  Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca Giulio","family":"Cossa","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.) University of Salento  Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4047-2876","authenticated-orcid":false,"given":"Carla","family":"Vetrugno","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.) University of Salento  Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Antonaci","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.) University of Salento  Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6535-3286","authenticated-orcid":false,"given":"Santo","family":"Marsigliante","sequence":"additional","affiliation":[{"name":"Department of Biological and Environmental Sciences and Technologies (Di.S.Te.B.A.) University of Salento  Lecce Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11302-013-9372-5"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.12.2175"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2004.11.027"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.11.086678"},{"key":"e_1_2_7_6_1","first-page":"S238","article-title":"Management of malignant pleural mesothelioma\u2014the European experience","volume":"6","author":"Opitz I","year":"2014","journal-title":"J. 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