Extracellular Regucalcin: A Potent Suppressor in the Cancer Cell Microenvironment.

Abstract

The regucalcin gene is located on the X chromosome, comprising seven exons and six introns. This gene and protein are expressed in various tissues and cells and is predominantly expressed in human liver, kidney, and adrenal tissues. Regucalcin gene expression is enhanced via a mechanism mediated by several signaling molecules and transcription factors. Regucalcin plays a multifunctional role in cellular regulation in maintaining cell homeostasis. In addition, regucalcin has been implicated in several metabolic disorders and diseases. In particular, regucalcin plays a role as a novel suppressor in several types of cancer patients. Increased expression of regucalcin suppresses the growth of human cancer cells, suggesting its pivotal role in suppressing tumor development. The survival time of cancer patients is prolonged with increased expression of regucalcin in the tumor tissues. The adhesion, migration, invasion, and bone metastatic activity of cancer cells are blocked by the overexpression of regucalcin, promoting dormancy in cancer patients. Interestingly, regucalcin is also found in human serum, suggesting its character as a novel biomarker in various diseases. This extracellular regucalcin has been shown to suppress human cancer cells' growth and bone metastatic activity. Thus, extracellular regucalcin may play a vital role as a suppressor of human cancer activity. Alteration of the serum regucalcin levels in physiological and pathophysiological conditions may influence the activity of cancer cells in the microenvironment. This review will discuss the potential role of extracellular regucalcin in cancer cell activity as a critical suppressor in the cancer microenvironment.