The Role οf Ion Channels in the Development and Progression of Prostate Cancer

Abstract

Numerous studies have firmly established the role of ion channels in essentially all basic cellular functions. Apart from their role in ion transport, they can form macromolecular complexes with adhesion proteins, and signaling molecules. Ion channels are not only responsible for cellular electrogenesis and excitability, but they also regulate the necessary conditions for tissue homeostasis, such as differentiation, proliferation and apoptosis.Although cancer is not officially classified as a channelopathy, it has been increasingly recognized that ion channel aberrations play an important role in virtually all cancer types.Ion channels can exert pro-tumorigenic activities due to genetic or epigenetic alterations, or as a response to molecular signals, such as growth factors, hormones, etc. Prostate cancer is the second leading cause of cancer-related death in men in the United States. Increasing evidence suggests that ion channels and pumps play a critical role in the regulation of prostate cancer cell proliferation, apoptosis evasion, migration, epithelial-to-mesenchymal transition and angiogenesis. There is also evidence suggesting that ion channels might play a role in treatment failure in prostate cancer. Hence, they represent promising targets for diagnosis, staging and treatment. Here, the role of major types of ion channels involved in the development and progression of prostate cancer were reviewed. Identifying the

The Emerging Role of Voltage-Gated Ion Channels in Cancer

“…This is also supported by the observation that specific genomic defects usually associated with cancer, sometimes do not accurately predict tumor aggressiveness, pointing towards the existence of additional drivers [8]. There is a growing body of evidence in the literature suggesting a pro-tumorigenic effect of various ion channel and pump aberrations [9]. Mutations or expression losses in ion channel genes, as well as abnormal expression/function is linked to several tumor types [10].…”

“…Changes in the ion composition inside the cells affect several cellular events and molecular pathways. One notable example is cell movement which requires an ion channelorchestrated sequence of cellular protrusions and retractions [9].…”

“…Ion channel activity is directly or indirectly involved in the pathogenesis of all cancer hallmarks, while several experimental and clinical studies suggest that their modulation may exert antitumor effects [9]. A notable example is the positive association between anesthetic drug use and increased overall survival in cancer patients.…”

“…A notable example is the positive association between anesthetic drug use and increased overall survival in cancer patients. Potential mechanisms have been proposed, including innate and adaptive immune system modulation, or a direct effect on ion channel signaling [9]. Interestingly, local anesthetics continue to inhibit the activity and function of voltage gated sodium channels beyond the intraoperative period [9].…”

Neuronal acid-sensing ion channel 1a regulates neuron-to-glioma synapses

“…K + channels govern a wide range of biological processes and play critical roles in a variety of diseases by controlling potassium flow across cell membranes (Zhorov, 2011). K + channels are selectively expressed in numerous tumor cells, including gliomas, and impact tumor biological processes, such as proliferation, apoptosis, differentiation, and invasions (Pardo and Stuhmer, 2014;Takayasu et al, 2020;Sakellakis and Chalkias, 2023). To evaluate the hypothesis that the deletion of Asic1a in neurons inhibits K + channel activity in glioma cells, we conducted a comprehensive analysis focused on voltageactivated K + channels.…”