The HIN-1 gene encoding a small, secreted protein is silenced due to methylation in a substantial fraction of breast, prostate, lung, and pancreatic carcinomas, suggesting a potential tumor suppressor function. The receptor of HIN-1 is unknown, but ligand-binding studies indicate the presence of high-affinity cell surface HIN-1 binding on epithelial cells. Here, we report that HIN-1 is a potent inhibitor of anchoragedependent and anchorage-independent cell growth, cell migration, and invasion. Expression of HIN-1 in synchronized cells inhibits cell cycle reentry and the phosphorylation of the retinoblastoma protein (Rb), whereas in exponentially growing cells, HIN-1 induces apoptosis without apparent cell cycle arrest and effect on Rb phosphorylation. Investigation of multiple signaling pathways revealed that mitogen-induced phosphorylation and activation of AKT are inhibited in HIN-1-expressing cells. In addition, expression of constitutively activate AKT abrogates HIN-1-mediated growth arrest. Taken together, these studies provide further evidence that HIN-1 possesses tumor suppressor functions, and that these activities may be mediated through the AKT signaling pathway.

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Over the past 50 years, our understanding of cancer has grown dramatically. Conceptual models that explain the tumor development process have been formulated. The biological characteristics that account for the behavior of tumor cells in experimental systems and in vivo and the genetic alterations that account for these changes have been catalogued in detail. Additionally, new preventative strategies and therapeutic agents using this wealth of information are now being formulated. In this chapter, we present a brief overview of our current understanding of cancer as a disease as well as give specific examples of some of the approaches being adopted to combat it.

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