Importance of Plasma Membrane Dynamics in Chemical-Induced Carcinogenesis

Xavier      Tekpli; Jorn      A. Holme; Odile      Sergent; Dominique      Lagadic-Gossmann

Abstract

In the last decade, a lot of patents have been filled regarding molecular biology and functions of cellular membranes. The membrane bilayer model has evolved from a static, passive, homogeneous barrier to a highly dynamic, asymmetric, heterogeneous structure composed of distinct domains. Changes in membrane fluidity and composition of microdomains have been proven to be involved in the regulation of many important physiological signaling pathways.

Recently, several xenobiotics, including various drugs and environmental pollutants, have been reported to change plasma membrane characteristics, thereby altering cell physiology. Interestingly, it has been suggested that a cross talk between chemical-induced cellular membrane effects and DNA damages may be important for the final mutation outcome of genotoxic chemicals. Thus, effects on plasma membrane remodeling may give additional mechanistic explanations to how certain chemicals exert their carcinogenic effect. With respect to such effects, recent patents suggest to focus on plasma membrane and its components like caveolin-1 for cancer screening and chemotherapy. Here, we review the effects of environmental toxicants on cellular plasma membrane structure and function, and further describe possible implication for health and disease.

Keywords: Carcinogenesis, caveolin, cell death, DNA damage, membrane alteration, reactive oxygen species, lipid rafts, angiogenesis, cytoskeleton, cell polarity