Regulation of Kinase Signaling Pathways by 64-Integrins and Plectin in Prostate Cancer

alpha 6 beta 4-integrins-integrins and plectin are the key structural components of hemidesmosomes that have been implicated in carcinogenesis and which are thus considered as potential cancer biomarkers and drug targets for anti-cancer therapies. In this review, we elaborate on the current knowledge of the kinase signaling pathways regulated by alpha 6 beta 4-integrins and plectin in the context of prostate cancer. We discuss an emerging scenario where hemidesmosomal alpha 6 beta 4-integrins and plectin function as tumor suppressors but adopt new oncogenic roles upon hemidesmosome disassembly in prostate cancer. Hemidesmosomes (HDs) are adhesive structures that ensure stable anchorage of cells to the basement membrane. They are formed by alpha 6 beta 4-integrin heterodimers and linked to intermediate filaments via plectin. It has been reported that one of the most common events during the pathogenesis of prostate cancer (PCa) is the loss of HD organization. While the expression levels of beta 4-integrins are strongly reduced, the expression levels of alpha 6-integrins and plectin are maintained or even elevated, and seem to promote tumorigenic properties of PCa cells, such as proliferation, invasion, metastasis, apoptosis- and drug-resistance. In this review, we discuss the potential mechanisms of how HD components might contribute to various cellular signaling pathways to promote prostate carcinogenesis. Moreover, we summarize the current knowledge on the involvement of alpha 6 beta 4-integrins and plectin in PCa initiation and progression.