sHsp as novel regulators of programmed cell death and tumorigenicity.

sHsp (small stress proteins) are molecular chaperones involved in cellular defence mechanisms against several different types of aggressions. These proteins also participate in essential physiological processes, such as regulation of cell cycle, differentiation, programmed cell death and tumorigenicity. For example, sHsp are transiently expressed during the cell division to differentiation transition and this phenomenon prevents differentiating cells from undergoing apoptosis. sHsp also protect against apoptosis induced by different conditions or agents, particularly anti-cancer drugs. Of interest, tumor cells usually express high levels of sHsp, and anti-cancer drugs, such as cisplatin, trigger the accumulation of sHsp. These proteins are also known to interfere with programmed cell death induced by TNF alpha and Fas ligand. Moreover, they enhance the growth of tumors in vivo. Taken together, these observations suggest that sHsp can allow cancerous cells to escape the immunosurveillance mediated by death ligands and can render these cells resistant to therapy. Hence, sHsp represent prime targets for therapeutic interventions. This review is focused on the role of sHsp in different aspects of the life and death of mammalian cells and on the role of these survival proteins in cancer.