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Inhibition of Cell Invasion by Targeting PLD

Farkaly, Terry C.

Abstract Details

2010, Master of Science (MS), Wright State University, Biochemistry and Molecular Biology.
Phospholipase D (PLD) is a crucial signaling enzyme involved in many cellular processes. The catalytic activity of PLD is essential for the production of Phosphatidic Acid (PA), a critical second messenger in cell signaling cascades downstream. Using the highly invasive rat mammary adenocarcinoma cell line mTLn3 as a metastatic model, we investigated the proficiency of these cells to invade using matrigels that mimic the basement membrane of the extracellular matrix (ECM), their activity through PLD enzymatic assays, as well as the potency of our potential inhibitors to inhibit PLD-mediated cell invasion and lipase activity. This study reveals that PLD-mediated cell invasion is dependent on protein-protein interactions with other cell signaling molecules such as Grb2 and Rac2 and their effect on lipase activity. Regulation of PLD2 activity by phosphorylation on tyrosine residue sites within its Phox domain are examined; in which we elucidate the effects of specific kinases EGFR, Jak3 and Src on cell invasion and enzymatic activity. Based off this approach, a therapeutic resolution will be proposed to diminish cell invasion in metastasis.
Julian Gomez-Cambronero, PhD (Committee Chair)
Michael Leffak, PhD (Committee Member)
Steven Berberich, PhD (Committee Member)
101 p.

Recommended Citations

Citations

  • Farkaly, T. C. (2010). Inhibition of Cell Invasion by Targeting PLD [Master's thesis, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1292449970

    APA Style (7th edition)

  • Farkaly, Terry. Inhibition of Cell Invasion by Targeting PLD. 2010. Wright State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1292449970.

    MLA Style (8th edition)

  • Farkaly, Terry. "Inhibition of Cell Invasion by Targeting PLD." Master's thesis, Wright State University, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=wright1292449970

    Chicago Manual of Style (17th edition)