CD44 EXPRESSION INDUCES CALCIUM INFLUX DECREASING EGR-1 EXPRESSION AND PROLIFERATION IN ACUTE LYMPHOCYTIC LEUKEMIA CELLS

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2014-03

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Racine, Ronny R.
Mummert, Mark E.

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Abstract

CD44 is a cell surface glycoprotein that serves as the major receptor for hyaluronan, aiding in trafficking and adhesion of immune cells. CD44 also serves as a recruitment platform for signaling molecules and has been shown to regulate proliferation. We have shown that CD44 expression in Jurkat T cells causes a decrease in proliferation. In our current study, we have observed that CD44 expression greatly increases the influx of calcium from extracellular sources. Calcium influx is necessary for the proliferation of T cells, but CD44 expressing Jurkat cells show a disrupted calcium homeostasis. Through use of calcium channel inhibitors we have shown that Jurkat T cells rely on calcium release activated calcium channels for influx. We have observed that CD44 induced excess calcium influx negatively regulates early growth response protein 1 expression, which is responsible for the decrease in proliferation. Our findings show for the first time that CD44 can influence the calcium signaling of leukemic T cells, impacting their proliferation and potentially making a less aggressive cancer cell. Purpose (a): CD44 is a cell surface glycoprotein that serves as the major receptor for hyaluronan, aiding in trafficking and adhesion of immune cells. CD44 also serves as a recruitment platform for signaling molecules and has been shown to regulate proliferation. We have shown that CD44 expression in Jurkat T cells causes a decrease in proliferation. Methods (b): In our current study, we have observed that CD44 expression greatly increases the influx of calcium from extracellular sources. Calcium influx is necessary for the proliferation of T cells, but CD44 expressing Jurkat cells show a disrupted calcium homeostasis. Through use of calcium channel inhibitors we have shown that Jurkat T cells rely on calcium release activated calcium channels for influx. Results (c): We have observed that CD44 induced excess calcium influx negatively regulates early growth response protein 1 expression, which is responsible for the decrease in proliferation. Conclusions (d): Our findings show for the first time that CD44 can influence the calcium signaling of leukemic T cells, impacting their proliferation and potentially making a less aggressive cancer cell.

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Research Appreciation Day Award Winner - 2014 Graduate School of Biomedical Sciences Awards, Department of Cell Biology - 1st Place Poster Award
Research Appreciation Day Award Winner - 2014 Graduate Student Association Awards - 3rd Place Poster

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