Cholesterol-rich lipid rafts mediate akt-regulated survival in prostate cancer cells.

Although cholesterol accumulation in tumors was first reported in the early20th century, the mechanistic implications of this observation are still obscure. Here we report that caveolin-negative human prostate cancer (LNCaP) cells contain cholesterol-rich lipid rafts that mediate epidermal growth factor (EGF)-induced and constitutive signaling through the Akt1 serine-threonine kinase. EGF receptor and Akt1 phosphorylation were inhibited and autonomous cell survival was reduced when the rafts were disrupted. Reconstitution of the rafts with cholesterol restored EGF receptor-->Akt1 axis signaling and cytoprotection from a phosphoinositide 3-kinase-dependent apoptotic signal. These results suggest that cholesterol present in membrane microdomains is a prominent mediator of survival in prostate cancer cells.