Abstract: Malignant tumors are characterized by excessive growth, immortalization, and metastatic spread, whereas benign tumors are subject to growth deregulation and immortalization without expressing gene products that mediate invasion. Gain-of-function mutations of oncogenes or loss-of-function mutations of tumor suppressor genes underlie excessive cell division. Activation of senescence suppressor genes or inactivation of senescence genes underlies immortalization. Based on the phenotypes of knockout mice for various confirmed metastasis genes, we have identified the genetic basis of metastasis formation as aberrant expression or splicing of a unique set of developmentally non-essential genes (stress response genes) that physiologically mediate the homing of immune system cells. Metastasis genes encode homing receptors, their ligands, and extracellular matrix-degrading proteinases, which jointly cause invasion and anchorage-independence. The specific interaction of homing receptors on the tumor cell surface and their cognate cytokine ligands mediates migration and invasion. The organ preference of metastasis formation is determined by the particular identity of the homing receptors expressed on the tumor cell surface and their ligands. Oncogenes act upstream of metastasis genes. Their signaling in cancer cells activates distinct genetic programs leading to cell cycle progression and invasiveness respectively. The identification of genes that direct cancer metastasis implicates their products candidate drug targets.

Brief Biography of the Speaker:
Georg F. Weber has made substantial contributions to the exploration of cancer dissemination by defining the genetic basis of metastasis formation as aberrant expression or splicing of stress response genes and by discovering the interaction between the molecules osteopontin and CD44. Georg F. Weber attended medical school in Wuerzburg, Germany. In 1988, he graduated and also completed his doctoral thesis. He worked at the Dana-Farber Cancer Institute, Harvard Medical School from 1990 through 1999. After a stint at Tufts University, 2000-2003, he moved to the University of Cincinnati, where he is currently on the faculty. Georg F. Weber has published over 60 scientific reports, including many in the most respected professional journals, and holds several patents. He is the author of various monographs, most recently a textbook on molecular oncology. While he continues to address fundamental questions, he is researching new venues of diagnosis and therapy of cancer dissemination. As a component of this mission, Georg F. Weber is the founder and Chief Executive Officer of MetaMol Theranostics, a company specialized in diagnosis and treatment of cancer metastasis.