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Phosphatidylinositol Remodeling through Membrane Bound O-acyl Transferase Domain-7 (MBOAT7) Promotes the Progression of Clear Cell Renal Cell Carcinoma (ccRCC)

Neumann, Chase K. A.
http://rave.ohiolink.edu/etdc/view?acc_num=case1586250046745924

Abstract Details

2020, Doctor of Philosophy, Case Western Reserve University, Molecular Medicine.
In the metabolism of cancer, phosphatidylinositols (PI) sit at the apex of signaling decisions and structure. PI phospholipids like other phospholipids can be synthesized via two major pathways: the Lands’ Cycle and the Kennedy Pathway. One key regulator of arachidonic acid-containing PI (AA-PI) levels in the Lands’ cycle remodeling pathway is membrane bound O-acyltransferase domain containing 7 (MBOAT7). For the first time in this work, MBOAT7 and AA-PI was found to be upregulated in clear cell Renal Cell Carcinoma (ccRCC) tumors compared to the normal adjacent tissue. The reduction in AA-PI leads to a decrease in tumor growth/formation, cellular proliferation, and cell migration. We also found that the implications of MBOAT7 deficiency extend to glycolysis and the Citric Acid cycle. Previously, cancer cell signaling research has focused on the terminal step in phosphoinositide (PIP3,4,5) production, which has been the focus of an entire class of small molecule inhibitors. Phosphoinositide signaling can play a critical role in cellular functions; many of these critical to cancer metabolism. However, my work demonstrates that the initial phosphatidylinositol generation through MBOAT7 is equally important to downstream phosphoinositide and therapeutically relevant for the treatment of ccRCC with potential implications for other cancers.
Oliver Wessely, PhD (Committee Chair)
Brown J. Mark, PhD (Advisor)
Lathia Justin, PhD (Committee Member)
McIntyre Thomas, PhD (Committee Member)
Ornstein Moshe, MD (Other)
117 p.
Biochemistry; Cellular Biology; Molecular Biology; Oncology
Cancer metabolism; Lipid metabolism; MBOAT7; Lands Cycle

Recommended Citations

Citations

  • Neumann, C. K. A. (2020). Phosphatidylinositol Remodeling through Membrane Bound O-acyl Transferase Domain-7 (MBOAT7) Promotes the Progression of Clear Cell Renal Cell Carcinoma (ccRCC) [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1586250046745924

    APA Style (7th edition)

  • Neumann, Chase. Phosphatidylinositol Remodeling through Membrane Bound O-acyl Transferase Domain-7 (MBOAT7) Promotes the Progression of Clear Cell Renal Cell Carcinoma (ccRCC). 2020. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1586250046745924.

    MLA Style (8th edition)

  • Neumann, Chase. "Phosphatidylinositol Remodeling through Membrane Bound O-acyl Transferase Domain-7 (MBOAT7) Promotes the Progression of Clear Cell Renal Cell Carcinoma (ccRCC)." Doctoral dissertation, Case Western Reserve University, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1586250046745924

    Chicago Manual of Style (17th edition)

case1586250046745924
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© 2020, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.