Cell Adhesion Group
Cell-Cell & Cell-Substrate Interactions
Steven K. Akiyama, Ph.D.
Cell adhesion and migration contribute to normal processes such as differentiation, embryonic development, and wound healing. Key mechanistic steps in these processes involve the interactions of extracellular glycoproteins (such as fibronectin, laminin and collagens) with specific adhesive receptors, the best characterized of which are the integrins, a family of heterodimeric complexes consisting of an alpha subunit and a beta subunit. Integrins are highly regulated receptors that can exist in either an active or inactive state. The dysregulation of cell adhesion and integrin-mediated signaling play key roles in a number of chronic and acute diseases that can result from human exposure to environmental toxicants including (but not limited to) cancer, inflammation, osteoporosis, and fibrotic diseases.
The overall goal of the Cell Adhesion Group is to characterize the molecular mechanisms of integrin-mediated adhesion processes, integrin activation and the resulting downstream processes induced by adhesive proteins such as fibronectin important for the control of proliferation, adhesion, migration and invasion of cells with a particular emphasis on human tumor cells.
The group’s current research examines one aspect of the intersection of cancer and the inflammatory response. Many environmental exposures result in increase cancer susceptibility and disregulation of the immune response and, hence, can exacerbate the etiology of malignant disease. By understanding molecular events that control cell adhesion, it should be possible to design agents (either those that promote or inhibit cell adhesion and signaling) to use in intervention and prevention strategies for the amelioration of human disease. The Cell Adhesion Group has been focused primarily on characterizing mechanisms of integrin activation involving adhesion receptor cross-talk between P-selectin cell surface binding proteins and beta-1integrins in tumor cells using two different endpoints: cell adhesion and cell migration. The group has found that binding of soluble P-selectin to certain tumor cells can activate integrin-mediated adhesion and spreading of these cells on the extracellular matrix glycoprotein, fibronectin. P-selectin induced integrin activation is the result of signal transduction in the form of a concomitant increase of phosphatidylinositol-3 kinase (PI-3 kinase) and p38 MAP kinase activities. The Cell Adhesion Group has recently identified nucleolin as a tumor cell surface, signaling binding protein for P-selectin.
Major areas of research:
- Modulation of cell-cell and cell-substrate adhesion
- Regulation of integrin-mediated tumor cell adhesion and migration by P-selectin binding to tumor cells
Steven Akiyama, Ph.D., leads the Cell Adhesion Group within the Laboratory of Molecular Carcinogenesis. He earned his Ph.D. in 1981 from the Department of Chemistry at Cornell University. He has published more than 70 peer-reviewed articles in leading biomedical journals as well as numerous book chapters and book reviews. He served as a Senior Investigator at the National Institute of Dental Research before joining NIEHS in 1996.