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Kathleen L. O'Connor, PhD

Cancer Center Member
Markey Research Programs:
    Cancer Cell Biology and Signaling

Associate Director for Cancer Education

Professor

Department of Molecular and Cellular Biochemistry
College of Medicine

Research Focus

My lab is interested in understanding how integrins and integrin-mediated signaling contribute to the late stages of carcinoma progression where cells acquire the ability to invade into the surrounding tissues. Integrin receptors, which link the extracellular matrix to the cytoskeleton and various signaling pathways, are essential for cells to sense and integrate cues from the extracellular matrix. Signaling from integrin receptors is critical for carcinoma cell invasion. One integrin species, the α6β4 integrin, can promote this process. My work has uncovered a link between integrin signaling and cyclic AMP metabolism. The metabolism of cAMP, i.e. both its generation and breakdown, is delicately balanced during invasion and is required for the control of the Rho family of small GTPases. We also find that the α6β4 integrin can promote the expression of pro-invasive genes, such as autotaxin, S100A4 and EGFR ligands amphiregulin and epiregulin. My long term goal is to understand the how integrins and integrin signaling control cAMP metabolism, RhoA, gene transcription and autocrine secretion to thereby contribute to the aggressive behavior of advanced cancers, including carcinomas of the breast, colon and pancreas. Read more about Dr. O'Connor's research on her department's profile page.

Contact Information

741 S. Limestone
University of Kentucky
Lexington, Kentucky 40506
859-323-7534
koco223@uky.edu

Key Publications

  1. O’Connor KL and Chen M. Dynamic Functions of RhoA in Tumor Cell Migration and Invasion. (Invited Review). Small GTPases 4(3):1-7; 2013.
  2. Chen M, Bresnick AR, O'Connor KL. 
Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells. 
Oncogene 32(32):3754-64, 2013.
  3. O'Connor KL, Chen M, Towers LN. Integrin α6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation.
 Am J Physiol Cell Physiol 302(3):C605-14, 2012.
  4. Chen M, Sastry SK, O'Connor KL. Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells.
 Am J Physiol Cell Physiol 300(5):C1155-63, 2011.
  5. Paulucci-Holthauzen AA, Vergara LA, Bellot LJ, Canton D, Scott JD, O'Connor KL. Spatial distribution of protein kinase A activity during cell migration is mediated by A-kinase anchoring protein AKAP Lbc. J Biol Chem 284(0):5956-67, 2009.

Five Most Recent Publications (via PubMed, based on researcher's ID and University of Kentucky)

1.  Zaytseva YY, Elliott VA, Rychahou P, Mustain WC, Kim JT, Valentino J, Gao T, O'Connor KL, Neltner JM, Lee EY, Weiss HL, Evers BM.
Cancer cell-associated fatty acid synthase activates endothelial cells and promotes angiogenesis in colorectal cancer.
Carcinogenesis. 2014 Jun;35(6):1341-51.
2.  Chen M, Knifley T, Subramanian T, Spielmann HP, O'Connor KL.
Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion.
PLoS One. 2014;9(2):e89892.
3.  Harrison SM, Knifley T, Chen M, O'Connor KL.
LPA, HGF, and EGF utilize distinct combinations of signaling pathways to promote migration and invasion of MDA-MB-231 breast carcinoma cells.
BMC Cancer. 2013;13:501.
4.  Chen M, Bresnick AR, O'Connor KL.
Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells.
Oncogene. 2013 Aug;32(32):3754-64.
5.  Chen M, Sastry SK, O'Connor KL.
Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells.
Am J Physiol Cell Physiol. 2011 May;300(5):C1155-63.