Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Abstract

The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional and posttranslational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

Abnormal Expression and Prognosis Value of COG Complex Members in Kidney Renal Clear Cell Carcinoma (KIRC)

“…N-acetylglucosaminyltransferases (MGAT1) regulated the tumour growth and invasion [25][26][27]. In addition, the sialyltransferase ST6GAL1 regulated the abnormal glycosylation of some tumour suppressor genes to promote tumourigenesis [28,29], suggesting that COG complex acts as upstream regulators of these genes to regulate their function in tumours. Moreover, glycosylation and trafficking defects in fibroblasts isolated from COG-deficient human patients have been found through several experimental approaches, suggesting that COG complex plays a key role in tumour metastasis by regulating protein glycosylation.…”

Serum Sialylation Changes in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Patients

“…Recent studies have demonstrated the role of ST6GALI in the malignant phenotype (growth, survival, angiogenesis, apoptosis, invasion, resistance to cell stress, chemoresistance). Increased ST6GAL1 activity is determined by genetic instability and epigenetic, transcriptional, and posttranslational factors [ 27 , 30 ].…”

“…The transfer of sialic acids is modulated by sialyltransferases, a group of glycosyltransferases divided into four families: β-galactoside α2,3-sialyltransferases (ST3Gal-I-VI), β-galactoside α2,6-sialyltransferases (ST6Gal-I and -II), GalNAc α2,6-sialyltransferases (ST6GalNAc-I-VI), and α2,8-sialyltransferases (ST8Sia-I-VI) [ 28 ]. During cell differentiation and neoplastic transformation, the expression of sialyltransferases undergoes substantial alterations resulting in phenotypic changes [ 27 , 28 , 29 , 30 ]. Sialyltransferases are well known as crucial modulators of several important processes such as cell-cell communication, cell-matrix interaction, cell adhesion, cell signaling, and trafficking [ 29 ].…”

Abnormal Glycosylation of Cancer Stem Cells and Targeting Strategies

“…Phosphorylated Akt also fosters S6 phosphorylation by mTORC1 leading to augmented protein synthesis, which triggers stemness through stimulated transcription (44). Expression of ST6 beta-galactoside alpha-2,6-sialyltransferase 1(ST6GAL1), which adds alpha2-6 lined sialic acid to glycosylated protein, is also upregulated in cancer malignancies specially in CSCs (79,80). ST6GAL1 expression corelated with other CSC markers in colorectal carcinoma (38,39) Renewal, cell proliferation and differentiation (27,40) samples from patient and induced chemoresistance (81).…”