{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:29:11Z","timestamp":1790220551585,"version":"4.1.0"},"reference-count":38,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2001,7,1]]},"abstract":"<jats:p> We have investigated cellular Ca<jats:sup>2+<\/jats:sup> regulation during A2058 human melanoma cell chemotaxis to type IV collagen (CIV). We have identified \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>-integrin as the primary mediator of A2058 cell response to CIV in vitro. Integrin ligation initiated a characteristic intracellular Ca<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>) response consisting of an internal release and a receptor-mediated Ca<jats:sup>2+<\/jats:sup> entry. Thapsigargin (TG) pretreatment drained overlapping and CIV-inducible internal Ca<jats:sup>2+<\/jats:sup> stores while initiating a store-operated Ca<jats:sup>2+<\/jats:sup> release (SOCR). CIV-mediated Ca<jats:sup>2+<\/jats:sup> entry was additive to TG-SOCR, suggesting an independent signaling mechanism. Similarly, ionophore application in a basal medium containing Ca<jats:sup>2+<\/jats:sup> initiated a sustained influx. Elevated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> from TG-SOCR or ionophore significantly attenuated cell migration to CIV by recruiting the Ca<jats:sup>2+<\/jats:sup>\/calcineurin-mediated signaling pathway. Furthermore, low [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub> induced by EGTA application in the presence of ionophore fully restored cell motility to CIV. Together, these results suggest that [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>signaling accompanying A2058 cell response to \u03b1<jats:sub>2<\/jats:sub>\u03b2<jats:sub>1<\/jats:sub>-integrin ligation is neither necessary nor sufficient and that elevated [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>i<\/jats:sub>downregulates cell motility via a calcineurin-mediated mechanism in A2058 cell chemotaxis to CIV. <\/jats:p>","DOI":"10.1152\/ajpcell.2001.281.1.c106","type":"journal-article","created":{"date-parts":[[2017,12,24]],"date-time":"2017-12-24T20:05:28Z","timestamp":1514145928000},"page":"C106-C113","source":"Crossref","is-referenced-by-count":14,"title":["[Ca<sup>2+<\/sup>]<sub>i<\/sub> as a potential downregulator of \u03b1<sub>2<\/sub>\u03b2<sub>1<\/sub>-integrin-mediated A2058 tumor cell migration to type IV collagen"],"prefix":"10.1152","volume":"281","author":[{"given":"Louis","family":"Hodgson","sequence":"first","affiliation":[{"name":"Department of Bioengineering, 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