Cancer Cell Biology and Signaling
Colleges & Departments:
College of Medicine, Department of Molecular and Cellular Biochemistry
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.
- Integrin α6β4 Upregulates Amphiregulin and Epiregulin through Base Excision Repair-Mediated DNA Demethylation and Promotes Genome-wide DNA Hypomethylation. Carpenter BL, Liu J, Wang C, and O’Connor KL. Scientific Reports. 7(1):6174. 2017.
- Elevated integrin α6β4 expression is associated with venous invasion and decreased overall survival in non-small cell lung cancer. Stewart RL, West D, Wang C, Weiss HL, Gal T, Durbin EB, O'Connor W, Chen M, O'Connor KL. Hum Pathol. 2016 August.
- S100A4 drives non-small cell lung cancer invasion, associates with poor prognosis, and is effectively targeted by the FDA-approved anti-helminthic agent niclosamide. Stewart RL, Carpenter BL, West DS, Knifley T, Liu L, Wang C, Weiss HL, Gal TS, Durbin EB, Arnold SM, O'Connor KL, Chen M. Oncotarget. 2016 June 7.
- Integrin α6β4 Promotes Autocrine Epidermal Growth Factor Receptor (EGFR) Signaling to Stimulate Migration and Invasion toward Hepatocyte Growth Factor (HGF). Carpenter BL, Chen M, Knifley T, Davis KA, Harrison SM, Stewart RL, O'Connor KL. J Biol Chem. 2015 November 6.
- Clinical significance of the integrin α6β4 in human malignancies. Stewart RL, O'Connor KL. Lab Invest. 2015 September.