Abstract
A large body of evidence accumulated during the last decade has revealed diverse roles of dysregulated water homeostasis in tumorigenesis. In particular, many tumors hypersecrete arginine vasopressin (AVP) causing hypoosmolar conditions associated with different cancers. Excess levels of free radicals and nonosmotic stimuli may act as signals in water homeostasis and induce the production and secretion of AVP. Hypoosmolar conditions cause alterations in the expression of many genes. Other alterations in hydration patterns may induce mutations and increase the levels of protein kinases to contribute to oncogenesis. Furthermore, AVP regulates the hypothalamic-pituitary-adrenal axis and angiogenesis, and its overproduction may contribute to tumor growth and metabolism. This review article describes a mechanism by which oxygen radical species and other free radicals act as signaling molecules that, in concert with increased AVP production and secretion, pleiotropically affect tumor growth and metabolism, resulting in dysregulated proliferation, cell cycle arrest, apoptosis, and genomic instability.
Highlights
Unrecognized vital roles of water in the body have been uncovered during the last decade [1, 2]
Dysregulated water homeostasis alters gene expression by rapidly upregulating genes such as LMO-4 that are associated with cancer [6, 7], alters hydration patterns to cause promiscuous binding of peptides to proteins and mutations [1, 8], and increases protein kinase production to contribute to oncogenesis and tumor progression [16]
More recent evidence suggests that reactive oxygen species (ROS) increase arginine vasopressin (AVP) production and secretion [21, 22] by the hypothalamoneurohypophyseal complex and through the noradrenaline-NO pathway, indicating that ROS and other free radicals act as signaling molecules that regulate various physiological processes of AVP, such as water homeostasis
Summary
Unrecognized vital roles of water in the body have been uncovered during the last decade [1, 2]. Dysregulated water homeostasis alters gene expression by rapidly upregulating genes such as LMO-4 that are associated with cancer [6, 7], alters hydration patterns to cause promiscuous binding of peptides to proteins and mutations [1, 8], and increases protein kinase production to contribute to oncogenesis and tumor progression [16]. Molecules and conditions that do not alter osmolarity but still stimulate AVP production and secretion include but are not limited to [19, 20] reactive oxygen species (ROS) [21, 22], tobacco smoke and nicotine [23,24,25], stress [26], and excessive alcohol consumption [27] These nonosmotic factors are considered to serve as signals that regulate water homeostasis [21, 22] and are commonly associated with an increased risk for cancer. Further research is required to determine whether increased estrogen receptor levels are a specific consequence of osmolarity
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