Abstract
The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed cation-permeable ion channel with intrinsic kinase activity that plays important roles in various physiological functions. Biochemical and electrophysiological studies, in combination with molecular analyses of TRPM7, have generated insights into its functions as a cellular sensor and transducer of physicochemical stimuli. Accumulating evidence indicates that TRPM7 channel-kinase is essential for cellular processes, such as proliferation, survival, differentiation, growth, and migration. Experimental studies in model organisms, such as zebrafish, mouse, and frog, have begun to elucidate the pleiotropic roles of TRPM7 during embryonic development from gastrulation to organogenesis. Aberrant expression and/or activity of the TRPM7 channel-kinase have been implicated in human diseases including a variety of cancer. Studying the functional roles of TRPM7 and the underlying mechanisms in normal cells and developmental processes is expected to help understand how TRPM7 channel-kinase contributes to pathogenesis, such as malignant neoplasia. On the other hand, studies of TRPM7 in diseases, particularly cancer, will help shed new light in the normal functions of TRPM7 under physiological conditions. In this article, we will provide an updated review of the structural features and biological functions of TRPM7, present a summary of current knowledge of its roles in development and cancer, and discuss the potential of TRPM7 as a clinical biomarker and therapeutic target in malignant diseases.
Highlights
The goal of this article is to review the molecular, cellular, and developmental biology of the transient receptor potential melastatin-subfamily member 7 (TRPM7) channel-kinase, as well as its implicated roles in cancer
The released kinase binds to transcription factors that contain Zn2+-binding domain and modifies chromatin through histone phosphorylation, whereas the remaining channel domain gets eliminated [49]. These results suggest that TRPM7’s channel controls cellular influx of Zn2+, which is in turn required for its chromatin-modifying kinase to regulate its target genes
Progressive advances have been made in deciphering the molecular basis of the activities of the TRPM7 channel and kinase
Summary
The goal of this article is to review the molecular, cellular, and developmental biology of the transient receptor potential melastatin-subfamily member 7 (TRPM7) channel-kinase, as well as its implicated roles in cancer. As a consequence of channel activation, cellular membrane becomes depolarized, and voltage-dependent ion channels permit transmembrane flow of cations such as Ca2+ and Mg2+ as well as modulation of the associated signaling pathways. These events form the basis of the functions of TRP channels as cellular sensors and transducers of various physical and chemical stimuli. We will review the emerging roles of TRPM7 in various types of cancer, and discuss its potential as a tumor biomarker and therapeutic target for prevention, early detection, and personalized treatment of malignant diseases
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