Neuroendocrine differentiation of LNCaP cells suggests: VDAC in the cell membrane is involved in the extrinsic apoptotic pathway

The primary structure of native human type-1 voltage dependent anion-selective channel/porin was presented twenty years ago, so was first data on its extra-mitochondrial expression in cell membranes of lymphocytes. Then, the channel had already entered cancer research as the docking molecule for hexokinase at outer mitochondrial membrane. Cell membrane standing porin met the cancer field only four years ago, when it was reported that normal and cancerous prostate cells from a single patient differed in the expression level of the channel. Meanwhile studies on a role of VDAC in cell differentiation, apoptosis, cancer and even pharmacology increase, mostly focused on porin in the outer membrane of mitochondria, but sometimes also pointing to the channel in the plasmalemma, e.g. prostate cancer cells on their way to neuroendocrine-differentiation. The synopsis presented discusses some recent papers on this issue, and argues in favor of considering voltage dependent anion-selective channel-cored volume regulated anion channel complexes in studies focused on apoptosis and cancer, where the channel might be part of the extrinsic cell death pathway. In this context, heed should also be given to the interaction of extra-mitochondrial porin and estrogen receptors alpha in cell membrane caveolae. Finally, it is insinuated to search for natural antibodies against type-1 porin, what in combination with other established markers might help in early diagnosis of prostate cancer. (C) 2009 Elsevier Inc. All rights reserved.