Kathleen L O'Connor

Bio / Education: 

B.S., James Madison University, 1988
Ph.D., Case Western Reserve University, 1996
Post-doctoral training, Harvard Medical School, 2001

Research Description: 

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 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.

PubMed Publications: 

  • Stewart, R.L.;O'Connor, K.L. "Integrin β4 is a controversial target for non-small cell lung cancer-reply." Human pathology 61, (2017): 223-224. [PubMed Link] | [ Full text ]
  • Kim, J.A.;Rosenthal, E.S.;Biswal, S.;Zafar, S.;Shenoy, A.V.;O'Connor, K.L.;Bechek, S.C.;Valdery Moura, J.;Shafi, M.M.;Patel, A.B.;Cash, S.S.;Westover, M.B. "Epileptiform abnormalities predict delayed cerebral ischemia in subarachnoid hemorrhage." Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology (2017): [PubMed Link] | [ Full text ]
  • Smith, T.J.;Wilson, M.A.;Karl, J.P.;Austin, K.;Bukhari, A.;Pasiakos, S.M.;O'Connor, K.L.;Lieberman, H.R. "Interstitial glucose concentrations and hypoglycemia during 2 days of caloric deficit and sustained exercise: a double-blind, placebo-controlled trial." Journal of applied physiology (Bethesda, Md. : 1985) 121, 5 (2016): 1208-1216. [PubMed Link] | [ Full text ]
  • Stewart, R.L.;Carpenter, B.L.;West, D.S.;Knifley, T.;Liu, L.;Wang, C.;Weiss, H.L.;Gal, T.S.;Durbin, E.B.;Arnold, S.M.;O'Connor, K.L.;Chen, M. "S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide." Oncotarget 7, 23 (2016): 34630-42. [PubMed Link] | [ Full text ]
  • Stewart, R.L.;West, D.;Wang, C.;Weiss, H.L.;Gal, T.;Durbin, E.B.;O'Connor, W.;Chen, M.;O'Connor, K.L. "Elevated integrin α6β4 expression is associated with venous invasion and decreased overall survival in non-small cell lung cancer." Human pathology 54, (2016): 174-83. [PubMed Link] | [ Full text ]
  • Stewart, R.L.;O'Connor, K.L. "Clinical significance of the integrin α6β4 in human malignancies." Laboratory investigation; a journal of technical methods and pathology 95, 9 (2015): 976-86. [PubMed Link] | [ Full text ]
  • Carpenter, B.L.;Chen, M.;Knifley, T.;Davis, K.A.;Harrison, S.M.;Stewart, R.L.;O'Connor, K.L. "Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF)." The Journal of biological chemistry 290, 45 (2015): 27228-38. [PubMed Link] | [ Full text ]
  • Zaytseva, Y.Y.;Elliott, V.A.;Rychahou, P.;Mustain, W.C.;Kim, J.T.;Valentino, J.;Gao, T.;O'Connor, K.L.;Neltner, J.M.;Lee, E.Y.;Weiss, H.L.;Evers, B.M. "Cancer cell-associated fatty acid synthase activates endothelial cells and promotes angiogenesis in colorectal cancer." Carcinogenesis 35, 6 (2014): 1341-51. [PubMed Link] | [ Full text ]
  • Chen, M.;Knifley, T.;Subramanian, T.;Spielmann, H.P.;O'Connor, K.L. "Use of synthetic isoprenoids to target protein prenylation and Rho GTPases in breast cancer invasion." PloS one 9, 2 (2014): e89892. [PubMed Link] | [ Full text ]
  • Harrison, S.M.;Knifley, T.;Chen, M.;O'Connor, K.L. "LPA, HGF, and EGF utilize distinct combinations of signaling pathways to promote migration and invasion of MDA-MB-231 breast carcinoma cells." BMC cancer 13, (2013): 501. [PubMed Link] | [ Full text ]
  • Chen, M.;Bresnick, A.R.;O'Connor, K.L. "Coupling S100A4 to Rhotekin alters Rho signaling output in breast cancer cells." Oncogene 32, 32 (2013): 3754-64. [PubMed Link] | [ Full text ]
  • O'Connor, K.L.;Chen, M.;Towers, L.N. "Integrin α6β4 cooperates with LPA signaling to stimulate Rac through AKAP-Lbc-mediated RhoA activation." American journal of physiology. Cell physiology 302, 3 (2012): C605-14. [PubMed Link] | [ Full text ]
  • Lee, S.;Qiao, J.;Paul, P.;O'Connor, K.L.;Evers, M.B.;Chung, D.H. "FAK is a critical regulator of neuroblastoma liver metastasis." Oncotarget 3, 12 (2012): 1576-87. [PubMed Link] | [ Full text ]
  • Gulhati, P.;Bowen, K.A.;Liu, J.;Stevens, P.D.;Rychahou, P.G.;Chen, M.;Lee, E.Y.;Weiss, H.L.;O'Connor, K.L.;Gao, T.;Evers, B.M. "mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways." Cancer research 71, 9 (2011): 3246-56. [PubMed Link] | [ Full text ]
  • Chen, M.;Sastry, S.K.;O'Connor, K.L. "Src kinase pathway is involved in NFAT5-mediated S100A4 induction by hyperosmotic stress in colon cancer cells." American journal of physiology. Cell physiology 300, 5 (2011): C1155-63. [PubMed Link] | [ Full text ]
  • Murillo, C.A.;Woodside, K.J.;Guo, Q.;Zhang, S.;O'Connor, K.L.;Hunter, G.C. "Integrin and matrix metalloproteinase expression in human carotid plaque." The Journal of surgical research 155, 1 (2009): 157-64. [PubMed Link] | [ Full text ]
  • Chen, M.;Sinha, M.;Luxon, B.A.;Bresnick, A.R.;O'Connor, K.L. "Integrin alpha6beta4 controls the expression of genes associated with cell motility, invasion, and metastasis, including S100A4/metastasin." The Journal of biological chemistry 284, 3 (2009): 1484-94. [PubMed Link] | [ Full text ]
  • Paulucci-Holthauzen, A.A.;Vergara, L.A.;Bellot, L.J.;Canton, D.;Scott, J.D.;O'Connor, K.L. "Spatial distribution of protein kinase A activity during cell migration is mediated by A-kinase anchoring protein AKAP Lbc." The Journal of biological chemistry 284, 9 (2009): 5956-67. [PubMed Link] | [ Full text ]
  • Cruz-Monserrate, Z.;O'Connor, K.L. "Integrin alpha 6 beta 4 promotes migration, invasion through Tiam1 upregulation, and subsequent Rac activation." Neoplasia (New York, N.Y.) 10, 5 (2008): 408-17. [PubMed Link] |
  • 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 (2007): C1927-33. [PubMed Link] | [ Full text ]
  • Cruz-Monserrate, Z.;Qiu, S.;Evers, B.M.;O'Connor, K.L. "Upregulation and redistribution of integrin alpha6beta4 expression occurs at an early stage in pancreatic adenocarcinoma progression." Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 20, 6 (2007): 656-67. [PubMed Link] | [ Full text ]
  • Li, J.;O'Connor, K.L.;Cheng, X.;Mei, F.C.;Uchida, T.;Townsend CM, J.;Evers, B.M. "Cyclic adenosine 5'-monophosphate-stimulated neurotensin secretion is mediated through Rap1 downstream of both Epac and protein kinase A signaling pathways." Molecular endocrinology (Baltimore, Md.) 21, 1 (2007): 159-71. [PubMed Link] | [ Full text ]
  • Paulucci-Holthauzen, A.A.;O'Connor, K.L. "Use of pseudosubstrate affinity to measure active protein kinase A." Analytical biochemistry 355, 2 (2006): 175-82. [PubMed Link] | [ Full text ]
  • Li, J.;O'Connor, K.L.;Greeley GH, J.;Blackshear, P.J.;Townsend CM, J.;Evers, B.M. "Myristoylated alanine-rich C kinase substrate-mediated neurotensin release via protein kinase C-delta downstream of the Rho/ROK pathway." The Journal of biological chemistry 280, 9 (2005): 8351-7. [PubMed Link] | [ Full text ]
  • Chen, M.;O'Connor, K.L. "Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells." Oncogene 24, 32 (2005): 5125-30. [PubMed Link] | [ Full text ]
  • Li, J.;O'Connor, K.L.;Hellmich, M.R.;Greeley GH, J.;Townsend CM, J.;Evers, B.M. "The role of protein kinase D in neurotensin secretion mediated by protein kinase C-alpha/-delta and Rho/Rho kinase." The Journal of biological chemistry 279, 27 (2004): 28466-74. [PubMed Link] | [ Full text ]
  • Farrow, B.;Rychahou, P.;O'Connor, K.L.;Evers, B.M. "Butyrate inhibits pancreatic cancer invasion." Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract 7, 7 (2003): 864-70. [PubMed Link] |
  • Farrow, B.;O'Connor, K.L.;Hashimoto, K.;Iwamura, T.;Evers, B.M. "Selective activation of PPARgamma inhibits pancreatic cancer invasion and decreases expression of tissue plasminogen activator." Surgery 134, 2 (2003): 206-12. [PubMed Link] | [ Full text ]
  • Farrow, B.;Rychahou, P.;Murillo, C.;O'Connor, K.L.;Iwamura, T.;Evers, B.M. "Inhibition of pancreatic cancer cell growth and induction of apoptosis with novel therapies directed against protein kinase A." Surgery 134, 2 (2003): 197-205. [PubMed Link] | [ Full text ]
  • Mercurio, A.M.;Bachelder, R.E.;Chung, J.;O'Connor, K.L.;Rabinovitz, I.;Shaw, L.M.;Tani, T. "Integrin laminin receptors and breast carcinoma progression." Journal of mammary gland biology and neoplasia 6, 3 (2001): 299-309. [PubMed Link] |
  • O'Connor, K.L.;Mercurio, A.M. "Protein kinase A regulates Rac and is required for the growth factor-stimulated migration of carcinoma cells." The Journal of biological chemistry 276, 51 (2001): 47895-900. [PubMed Link] | [ Full text ]
  • Mercurio, A.M.;Bachelder, R.E.;Rabinovitz, I.;O'Connor, K.L.;Tani, T.;Shaw, L.M. "The metastatic odyssey: the integrin connection." Surgical oncology clinics of North America 10, 2 (2001): 313-28, viii-ix. [PubMed Link] |
  • O'Connor, K.L.;Nguyen, B.K.;Mercurio, A.M. "RhoA function in lamellae formation and migration is regulated by the alpha6beta4 integrin and cAMP metabolism." The Journal of cell biology 148, 2 (2000): 253-8. [PubMed Link] | [ Full text ]
  • Culp, L.A.;Lin, W.;Kleinman, N.R.;O'Connor, K.L.;Lechner, R. "Earliest steps in primary tumor formation and micrometastasis resolved with histochemical markers of gene-tagged tumor cells." The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 46, 5 (1998): 557-68. [PubMed Link] | [ Full text ]
  • O'Connor, K.L.;Shaw, L.M.;Mercurio, A.M. "Release of cAMP gating by the alpha6beta4 integrin stimulates lamellae formation and the chemotactic migration of invasive carcinoma cells." The Journal of cell biology 143, 6 (1998): 1749-60. [PubMed Link] | [ Full text ]
  • O'Connor, K.L.;Culp, L.A. "Quantitation of two histochemical markers in the same extract using chemiluminescent substrates." BioTechniques 17, 3 (1994): 502-6, 508-9. [PubMed Link] |
  • Lin, W.C.;O'Connor, K.L.;Culp, L.A. "Complementation of two related tumour cell classes during experimental metastasis tagged with different histochemical marker genes." British journal of cancer 67, 5 (1993): 910-21. [PubMed Link] |