The study, led by Associate Professor Peiqing Sun and Professor Jiahuai Han of The Scripps Research Institute, is being published on January 26, 2007 in the journal Cell.
The research focused on signaling pathways that mediate an anti-tumor defense response called senescence, or cellular aging. The research, which was conducted in both human cell culture and rodent models with skin cancer or lymphoma, identified one essential element of this anti-tumor response, namely, p38-regulated/activated protein kinase (PRAK). Previous to this research, PRAK's physiological functions had been poorly understood.
"In uncovering this basic mechanism, we've advanced our knowledge in terms of how cancers develop," Sun said. "More importantly, we have identified a pathway in normal cells that, when activated, can inhibit tumor development. This lays the groundwork for new cancer therapy--for future drug development to artificially activate this pathway in cancer cells."
The human body has several built-in mechanisms that prevent cancer development. One is cell death, or apoptosis. Another is premature senescence, a recently identified tumor-restricting response that permanently stops cell proliferation.
"A normal cell stops dividing when it gets old," Sun explained. "This is referred to as senescence of a cell. A young cell will become senescent prematurely when it acquires a mutation that activates an oncogene. This is one of the ways our body tries to eliminate cells that might become cancerous."
In previous research that set the stage for this current project, Sun's lab worked to identify the signaling cascade that mediates ras-induced premature senescence (ras is an oncogene, a gene that, when activated by mutations, causes cancer by transducing unrestricted growth signals). Using human cells in culture, Sun's team showed that the p38 mitogen-activated protein (MAP) kinase is required for ras to induce senescence in cell cul
Contact: Keith McKeown
Scripps Research Institute