The functional role of DAB2IP, a homeostatic factor, in prostate cancer

Maintenance of cellular architecture and normal physiologic functioning of the prostatic epithelium is dependent on androgen. Cell proliferation and cell differentiation in normal prostatic gland maintains a homeostasis. This homeostatic control is impaired in prostate cancer (PCa) cells. Therefore, dissecting the mechanism of homeostatic machinery will provide a better understanding of PCa and allow us to formulate effective strategies for cancer therapy. One of the most exciting developments in oncology has been the step-by-step construction of signaling cascade that traces the path of extracellular stimuli, all the way from the external membrane to the cell nucleus. DAB2IP was first identified as a unique RAS-GTPase activating protein from the basal cell population in prostate. Loss of DAB2IP is frequently detected in PCa. DAB2IP modulates different signal cascades associated with cell proliferation, survival, and apoptosis. Restoring DAB2IP expression in PCa can inhibit cancer metastasis by preventing epithelialto- mesenchymal transition that is considered to be a cell de-differentiation process. In addition, DAB2IP can inhibit angiogenesis by enhancing endothelial apoptosis and/or inhibiting vascular growth factor and its receptor expression. Consistent with these findings, DAB2IP can also inhibit the onset of the stem cell phenotype of PCa cells. Taken together, DAB2IP appears to be a key factor in controlling homeostasis of prostatic epithelium.