B4GALT family mediates the multidrug resistance of human leukemia cells by regulating the hedgehog pathway and the expression of p-glycoprotein and multidrug resistance-associated protein 1

Abstract

β-1, 4-Galactosyltransferase gene (B4GALT) family consists of seven members, which encode corresponding enzymes known as type II membrane-bound glycoproteins. These enzymes catalyze the biosynthesis of different glycoconjugates and saccharide structures, and have been recognized to be involved in various diseases. In this study, we sought to determine the expressional profiles of B4GALT family in four pairs of parental and chemoresistant human leukemia cell lines and in bone marrow mononuclear cells (BMMC) of leukemia patients with multidrug resistance (MDR). The results revealed that B4GALT1 and B4GALT5 were highly expressed in four MDR cells and patients, altered levels of B4GALT1 and B4GALT5 were responsible for changed drug-resistant phenotype of HL60 and HL60/adriamycin-resistant cells. Further data showed that manipulation of these two gene expression led to increased or decreased activity of hedgehog (Hh) signaling and proportionally mutative expression of p-glycoprotein (P-gp) and MDR-associated protein 1 (MRP1) that are both known to be related to MDR. Thus, we propose that B4GALT1 and B4GALT5, two members of B4GALT gene family, are involved in the development of MDR of human leukemia cells, probably by regulating the activity of Hh signaling and the expression of P-gp and MRP1.

Multifaceted roles of 5′-regulatory region of the cancer associated gene B4GALT1 and its comparison with the gene family

“…Furthermore, B4GALT1 has been strongly linked with multidrug resistance (8,16), tumor sensitivity to cisplatin (17,18) and promotion of cell death signaling pathways (19). Additionally, the gene undergoes promoter methylation in several cancer types and consequent silencing of the gene (13,20,21).…”

“…The two isoforms are type II membrane-bound glycoproteins and reside in Golgi apparatus and a portion of the longer protein functions on the cell surface as a recognition molecule by binding with appropriate glycoside substrates (5). Consequently, the B4GALT1 plays important roles in numerous physiological and pathological processes such as inflammation, sperm-egg interaction, embryogenesis, and morphogenesis, development of the central nervous system, cell migration, cancer progression and metastasis (6)(7)(8).…”

Prognostic significance of ABCB1 in stage I lung adenocarcinoma

“…CSCs exhibit similar properties to those of normal stem cells, suggesting that these signaling pathways are important in maintaining CSCs in a variety of cancers, including lung (5,27). Previous studies reported that ABCB1 expression was affected by the above signaling pathways (28)(29)(30). However, the association between ABCB1 and these signaling pathways should be further confirmed in NSCLC patients.…”

Glycosylation is a global target for androgen control in prostate cancer cells

“…Linked to adverse outcome in patients with non-metastatic clear cell renal cell carcinoma . Associated with multi-drug resistance in leukemia (Zhou et al 2013) Upregulated by TNFα in prostate cancer cells -role in motility and invasion (Radhakrishnan et al 2011) …”

“…B4GALT1 transfers a galactose residue to terminal N-acetylglucosamine and is involved in the late processing of N-glycans. Upregulated B4GALT1 can predict adverse outcome in patients with non-metastatic clear cell renal cell carcinoma and is associated with multi-drug resistance in leukaemia (Zhou et al 2013). In prostate cancer cells, B4GALT1 can be upregulated by TNFα and is thought to have a role in cell motility and invasion (Radhakrishnan et al 2011).…”