Left to right: Adriana Paulucci-Holthauzen, Karla Alverez, Nicole Towers, Zobeida Cruz-Monserrate, Marsha Tallman, Kathy O’Connor and Min Chen
Kathleen O'Connor, Ph.D.
Departments of Surgery and
Biochemistry & Molecular Biology
Director, Cancer Cell Biology Track
I am 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
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 it 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
integrin can promote the expression of pro-invasive genes, such as autotaxin. My long term goal
understand the how integrins and integrin signaling
control cAMP metabolism and gene transcription and thereby contribute to the aggressive
behavior of advanced cancers, including carcinomas of the breast, colon and pancreas.
Spatial distribution of PKA activity during cell migration is mediated by kinase anchoring protein AKAP Lbc. Paulucci-Holthauzen AA, Vergara LA, Bello LJ, Canton D, Scott JD, O'Connor KL. J Biol Chem. 2008 Dec 23. [Epub ahead of print]
Integrin alpha 6beta 4 controls the expression of genes associated with cell motility, invasion and metastasis including S100A4/metastasin. Chem M, Sinha M, Luxon BA, Bresnick AR, O'Connor KL. J Biol Chem. 2008 Nov 14. [Epub ahead of print]
Cruz-Monserrate, Z and K.L. O’Connor. Integrin alpha 6 beta 4 promotes migration, invasion through Tiam1 upregulation, and subsequent Rac activation. Neoplasia. 2008 May;10(5):408-17.
Chen, M., Towers, L.N., O’Connor, K.L. LPA2 (EDG4) mediates Rho-dependent chemotaxis with lower efficacy than LPA1 (EDG2) in breast carcinoma cells. American Journal of Physiology—Cell Physiology 292(5):C1927-33; 2007.
O’Connor, K.L. Rac GTPase and cyclic nucleotides; Fitting cGMP into the cell migration machinery. Cell Science Reviews. 3 (4) (ISSN 1743-8130; 2007.
Cruz-Monserrate, Z., Qiu, s., Evers, B.M., O’Connor, K.L. Upregulation and redistribution of integrin α6β4 expression occurs at an early stage in pancreatic adenocarcinoma progression. Mod. Pathol. 20:656-67; 2007. [Epub April 6, 2007].
Paulucci-Holthauzen AA and O'Connor KL. Use of
pseudosubstrate affinity to measure active protein kinase A.
355(2):175-82, 2006; Epub 2006 Jun 19. PMID: 16842735 [PubMed - in process].
Chen M and O’Connor KL. Integrin
promotes expression of autotaxin/ENPP2 autocrine motility factor in breast ductal carcinoma
cells. Oncogene 24:5125-30, 2005.
Mercurio AM, Bachelder RE, Rabinovitz I, O’Connor KL, Tani T, Shaw LM. The metastatic
odyssey: The integrin connection. Surgical Oncology Clinics of North America. 10:313-28, 2001.
Mercurio AM, Bachelder RE, Chung J, O'Connor KL, Rabinovitz I, Shaw LM, Tani T.
Integrin laminin receptors and breast carcinoma progression. Journal of Mammary Gland Biology
and Neoplasia. 6:299-309, 2001.
KL, Mercurio AM. Protein
Kinase A regulates Rac and is required for the growth factor-stimulated migration of carcinoma
cells. J Biol Chem 276:47895-47900, 2001.
O'Connor KL, Nguyen B-K, Mercurio AM. RhoA function in lamellae formation and
migration is regulated by the
integrin and cAMP metabolism. J Cell Biol 148:253-258, 2000.
O'Connor KL, Shaw LM, Mercurio AM. Release of cAMP gating by the
integrin stimulates lamellae formation and the chemotactic migration of invasive carcinoma
cells. J Cell Biol 143:1749-1760, 1998.