Kenneth L. van Golen, Ph.D.
Assistant Professor
van Golen
Phone: (302) 831-2669
Fax: (302) 831-2281
Lab phone: (302) 831-8922
Email: klvg@udel.edu
Office: 320 Wolf Hall
Lab: 355-357 Wolf Hall
Address:
Department of Biological Sciences
Wolf Hall
University of Delaware
Newark, DE 19716
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Education
- B.S. - Michigan State University
- Ph.D. - University of Texas, Health Science Center
- Postdoctoral - University of Michigan
Research Interests
The Rho GTPases comprise a group of 23 small GTP binding proteins that play a significant role in nearly every cellular process. One of the most characterized roles of the Rho proteins is their ability to reorganize the cell cytoskeleton. Signals from the extracellular environment, transduced through growth factor receptors and/or cell adhesion molecules leads to the coordinated activation of Rho proteins and reorganization of the cytoskeleton. In turn, this leads to changes in cells shape, polarity, migratory and invasiveness.
The potent ability of the Rho proteins to affect cell migration and invasion has many implications for the dissemination and spread of cancer and in normal processes such as development and immunity. Our primary interest is in the role of the Rho GTPases in conferring the metastatic phenotype to aggressive cancers.
In 1999 our laboratory found that RhoC GTPase, one member of the Rho family, was overexpressed in inflammatory breast cancer, a particularly aggressive form of breast cancer which spreads rapidly through the dermal lymphatics of the breast. Later, we found that RhoC over expression was a prognostic marker for metastasis in small breast tumors (<1 cm in size). Since then we have begun to look at how RhoC confers a metastatic phenotype to inflammatory breast cancer and how it interacts with other Rho GTPases. Our studies have expanded to include pancreatic cancer and prostate cancer bone metastasis.
A complete understanding of how the Rho proteins, particularly RhoC, can influence progression of a cancer cell to become metastatic is key to the development of anti-metastatic therapies. To facilitate this we have developed a RhoC transgenic mouse. This mouse has a tumor phenotype but more interestingly it has a neurological phenotype which is yet undetermined. Our ultimate goal is to detail the Rho pathways, determining the choke points and developing inhibitors that can be used as adjuvant anti-metastatic therapies.
Current Projects
- The role of Rho GTPases in prostate cancer bone metastasis - The goal of this project is to understand the contribution of individual Rho GTPases during the process of binding to bone marrow endothelial cells, tumor cell diapedesis (transendothelial cell migration) and invasion through the bone stroma.
- Activation of RhoC GTPase in inflammatory breast cancer - The goal of this project is to understand the interaction of RhoC GTPase with other molecules which could influence its activation. In particular we are studying the role of RhoC with Akt/Protein Kinase B and with the scaffolding molecule caveolin-1.
- The contribution of RhoC GTPase to pancreatic cancer invasion and metastasis - The goal of this project is to understand how RhoC contributes to the formation of pancreatic cancer intraductal extensions and metastasis.
- The RhoC transgenic mouse - Although all of our projects use the RhoC transgenic mouse as a model, this mouse also displays a neurological phenotype. The mice are easily agitated, their circadian rhythms are altered and they spin. The goal of this project is to characterize this defect.
Selected Publications
- Cooper CR, Graves B, Pruitt F, et al. Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF-alpha. J Cell Biochem. 2008;104(6):2298–2309.
- Hall CL, Dubyk CW, Riesenberger TA, Shein D, Keller ET, van Golen KL. Type I collagen receptor (alpha2beta1) signaling promotes prostate cancer invasion through RhoC GTPase. Neoplasia. 2008;10(8):797–803.
- Miles FL, Pruitt FL, van Golen KL, Cooper CR. Stepping out of the flow: capillary extravasation in cancer metastasis. Clin Exp Metastasis. 2008;25(4):305–324.
- Sequeira L, Dubyk CW, Riesenberger TA, Cooper CR, van Golen KL. Rho GTPases in PC-3 prostate cancer cell morphology, invasion and tumor cell diapedesis. Clin Exp Metastasis. 2008;25(5):569–579.
- van Golen KL, Ying C, Sequeira L, et al. CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase Rac. J Cell Biochem. 2008;104(5):1587–1597.
- Hall CL, Dai JL, van Golen KL, Keller ET, Long MW. Type I collagen receptor (alpha 2 beta 1) signaling promotes the growth of human prostate cancer cells within the bone. Cancer Res. 2006;66(17):8648–8654.
- Van den Eynden GG, Van Laere SJ, Van der Auwera I, et al. Overexpression of caveolin-1 and -2 in cell lines and in human samples of inflammatory breast cancer. Breast Cancer Res Treat. 2006;95(3):219–228.
- van Golen CM, Schwab TS, Kim B, et al. Insulin-like growth factor-I receptor expression regulates neuroblastoma metastasis to bone. Cancer Res. 2006;66(13):6570–6578.
- van Golen KL. Is caveolin-1 a viable therapeutic target to reduce cancer metastasis? Expert Opin Ther Targets. 2006;10(5):709–721.
- Van Laere SJ, Van den Eynden GG, Van der Auwera I, et al. Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling. Breast Cancer Res Treat. 2006;95(3):243–255.
- Yao H, Dashner EJ, van Golen CM, van Golen KL. RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility. Oncogene. 2006;25(16):2285–2296.
- Zhang L, Chenwei L, Mahmood R, et al. Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer. Cancer Res. 2006;66(2):898–906.
- Kleer CG, Griffith KA, Sabel MS, et al. RhoC-GTPase is a novel tissue biomarker associated with biologically aggressive carcinomas of the breast. Breast Cancer Res Treat. 2005;93(2):101–110.
- Lin M, DiVito MM, Merajver SD, Boyanapalli M, van Golen KL. Regulation of pancreatic cancer cell migration and invasion by RhoC GTPase and caveolin-1. Mol Cancer. 2005;4(1):21.
- Radunsky GS, van Golen KL. The current understanding of the molecular determinants of inflammatory breast cancer metastasis. Clin Exp Metastasis. 2005;22(8):615–620.
- van Golen KL, Bao LW, DiVito MM, Wu ZF, Prendergast GC, Merajver SD. Reversion of RhoC GTPase-induced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor. Mol Cancer Ther. 2002;1(8):575–583.
- van Golen KL, Wu ZF, Qiao XT, Bao LW, Merajver SD. RhoC GTPase, a novel transforming oncogene for human mammary epithelial cells that partially recapitulates the inflammatory breast cancer phenotype. Cancer Res. 2000;60(20):5832–5838.
- van Golen KL, Davies S, Wu ZF, et al. A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. Clin Cancer Res. 1999;5(9):2511–2519.
- van Golen KL, Wu ZF, Bao LW, Merajver SD. RhoC GTPase induces a motile and invasive phenotype in inflammatory breast cancer. Clin Exp Metastasis. 1999;17(9):745.