Selenoproteins in colon cancer

Abstract

Selenocysteine-containing proteins (selenoproteins) have been implicated in the regulation of various cell signaling pathways, many of which are linked to colorectal malignancies. In this in-depth excurse into the selenoprotein literature, we review possible roles for human selenoproteins in colorectal cancer, focusing on the typical hallmarks of cancer cells and their tumor-enabling characteristics. Human genome studies of single nucleotide polymorphisms in various genes coding for selenoproteins have revealed potential involvement of glutathione peroxidases, thioredoxin reductases, and other proteins. Cell culture studies with targeted down-regulation of selenoproteins and studies utilizing knockout/transgenic animal models have helped elucidate the potential roles of individual selenoproteins in this malignancy. Those selenoproteins, for which strong links to development or progression of colorectal cancer have been described, may be potential future targets for clinical interventions.

Potential relationship between the selenoproteome and cancer

“…A study in Japan showed that GPX1, GPX3 and SELENOP were decreased and GPX2 was increased in colorectal cancer (CRC) ( 22 ). A study reviewed by Peters et al found that the redox homeostasis related selenoproteins GPX1-4, TXNRD1, SELENOF and SELENOP, and the WNT/β-catenin signalling pathway associated selenoproteins DIO3, GPX2, TXNRD3 and SELENOP may effect CRC risk and development ( 23 ). To the best of our knowledge, there are many selenoproteins whose roles in CRC are unknown ( 23 ).…”

“…A study reviewed by Peters et al found that the redox homeostasis related selenoproteins GPX1-4, TXNRD1, SELENOF and SELENOP, and the WNT/β-catenin signalling pathway associated selenoproteins DIO3, GPX2, TXNRD3 and SELENOP may effect CRC risk and development ( 23 ). To the best of our knowledge, there are many selenoproteins whose roles in CRC are unknown ( 23 ). These observations indicate that the selenoproteomes which exhibited significant changes in this study are a promising research target, which should have high priority.…”

“…Of particular interest are genes associated with survival, such as GPX4 and GPX8. Although there was no observed relationship between SNV and colorectal cancer/colon adenocarcinoma risk based on big genomic data ( 24 ), the SNV of GPX1, GPX2, GPX4, TXNRD1, TXNRD2, TXNRD3, SELENOF, SELENOP, SELENOS and SELENOW have been well studied in CRC, and the SNV of SELENOP and SELENOS had a strong effect on CRC risk ( 23-25 ). For colon adenocarcinoma, the top eight potential risk selenoprotein-related genes for SNV analysis were SELENOP, TXNRD1, DIO3, SELENOO, SEPHS1, SCLY, TXNRD2 and SELENOI ( Fig.…”

Release of reactive selenium species from phthalic selenoanhydride in the presence of hydrogen sulfide and glutathione with implications for cancer research

“…1,2 Both Se-containing compounds and the Se atom present in the active sites of 25 mammalian selenoproteins identified so far participate in key cellular and physiological processes, as well as diseases such as cancer, inflammation, immunity, type 2 diabetes or liver diseases. [3][4][5][6][7][8] However, the molecular mechanism of action is not fully understood yet for some of these selenoproteins.…”

Histological analysis of rat prostate under exogenous testosterone and low dose of oral selenium administration

“…Several studies relating selenium supplementation with immune response, using tumors as a model, have shown that this nutrient in many cases can reduce or inhibit tumor growth, both in humans an rodent models 14,15 . Decreased in incidence of cancer by selenium intake has been shown in epidemiological studies in humans and other animals with selenium supplementation showed a reduction in tumor incidence or tumor size.…”