Lu-Gang Yu

University of Liverpool | UoL · Institute of Translational Medicine

Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells to vascular endothelium in vitro and experimental metas...

Purpose: Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer and in particular those with metastasis, on cytokine secretion from the bloo...

The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have previously shown that circulating galectin-3, that is increased by up to 30-fold in cancer patients, promotes blood-borne metastasis...

Epidermal growth factor receptor (EGFR) is an important regulator of epithelial cell growth and survival in normal and cancerous tissues and is a principal therapeutic target for cancer treatment. EGFR is associated in epithelial cells with the heavily glycosylated transmembrane mucin protein MUC1, a natural ligand of galectin-3 that is overexpress...

Formation of tumour cell aggregation/emboli prolongs the survival of circulating tumour cells in the circulation, enhances their physical trapping in the micro-vasculature and thus increases metastatic spread of the cancer cells to remote sites. It shows here that the presence of the galactoside-binding galectin-3, whose concentration is markedly i...

Galectin-2 is a prototype member of the galactoside-binding galectin family. It is predominately expressed in the gastrointestinal tract but is also detected in several other tissues such as the placenta and in the cardiovascular system. Galectin-2 expression and secretion by epithelial cells has been reported to contribute to the strength of the m...

Melanoma cell adhesion molecule (MCAM, CD146, MUC18) is a heavily glycosylated transmembrane protein and a marker of melanoma metastasis. It is expressed in advanced primary melanoma and metastasis but rarely in benign naevi or normal melanocytes. More and more evidence has shown that activation of the MCAM on cell surface plays a vital role in mel...

Matrix metalloproteinase-13 (MMP-13) is a member of the Matrix metalloproteinases (MMPs) family of endopeptidases. MMP-13 is produced in low amounts and is well-regulated during normal physiological conditions. Its expression and secretion are, however, increased in various cancers, where it plays multiple roles in tumour progression and metastasis...

Simple Summary: C1GalT1 is one of the enzymes that catalyze the addition of sugar residues to proteins (protein glycosylation). It specifically controls the synthesis and formation of a special di-saccharide structure Galβ1,3GalNAcα-Ser/Thr, which occurs predominately in cancer but rarely in normal cells. Recent studies have shown that C1GalT1 is o...

Peanut agglutinin (PNA) is a carbohydrate-binding protein in peanuts that accounts for ~0.15% peanut weight. PNA is highly resistant to cooking and digestion and is rapidly detectable in the blood after peanut consumption. Our previous studies have shown that circulating PNA mimics the actions of endogenous galactoside-binding protein galectin-3 by...

Tumor-associated macrophages (TAMs) have been shown to be associated with poor prognosis of cancer and are predominately localized in the hypoxia regions of tumor. We demonstrated in this study that hypoxia increases the synthesis and secretion of galectin-3 by TAMs. The increased expression of galectin-3 in TAMs was seen to be associated with nucl...

Angiogenesis and vasculogenic mimicry (VM) are the main causes of tumor metastasis and recurrence. In this study, we investigated the antiangiogenesis and anti-VM formation of a novel microtubule depolymerizing agent, DHPAC, as well as combretastatin A4 (CA4, a combretastatin derivate) in non-small-cell lung cancer (NSCLC), subsequently elucidating...

The inflammatory bowel diseases (IBD), which include mainly Crohn’s disease (CD) and ulcerative colitis (UC), are common chronic inflammatory conditions of the digestive system. The diagnosis of IBD relies on the use of a combination of factors including symptoms, endoscopy and levels of serum proteins such as C-reactive protein (CRP) or faecal cal...

The β-galactoside-binding protein, galectin-3, is extensively involved in cancer development, progression and metastasis through multiple mechanisms. Inhibition of the galectin-3-mediated actions is increasingly considered as a promising therapeutic approach for cancer treatment. Our early studies have identified several novel galectin-3 binding in...

The galactoside-binding protein galectin-3 is commonly overexpressed by cancer cells and promotes cancer progression and metastasis. Over the past few years, evidence has emerged that galectin-3 is also overexpressed in several metabolic malfunction conditions such as diabetes, obesity and atherosclerosis and is involved in the regulation of the oc...

Galectins are involved in the regulation of divergent physiological and pathological processes and are increasingly recognized to play important roles in a number of diseases. However, a simple and effective way in assessing galectin-ligand interactions is lacking. Our examination of the sequence of all 12 human galectin members reveals the presenc...

Introduction Non-invasive biomarkers currently available in clinic in (i) accurately diagnosing IBD and (ii) in determining disease activity in established IBD all show poor sensitivity and substantial limitation. In this study, we investigated whether levels of serum galectins, a family of 15 galactoside-binding proteins, could be used as potentia...

TF antigen binding lectins from dietary sources PNA, ACA, ABL, JAC, and SRL from Sclerotium rolfsii have been reported to induce diverse effects on cancer cell proliferation by different mechanisms. This study aimed to compare effects of these lectins on growth and cell cycle progression in colon cancer HT29 and SW620 cells. As reported SRL, ABL, a...

Tumor cell-endothelial adhesion is one of the key steps in tumor cell haematogenous dissemination in metastasis and was previously shown to be mediated by interaction of galectin-3 with the transmembrane mucin protein MUC1. In this study, the effect of exogenous as well as endogenous galectin-3 on adhesion of two cell lines (low MUC1-expressing hum...

Multidrug resistance (MDR) is one of major obstacles to effective chemotherapeutic treatment of cancer. This study showed that DHPAC, 2-(6-ethoxy-3-(3-ethoxyphenylamino) -1-methyl-1,4-dihydroindeno[1,2-c]pyrazol-7-yloxy) acetamide, a novel compound that binds to the same site on microtubules as colchicine, has high anti-tumour activity in vincristi...

Hepatocellular carcinoma (HCC) has poor prognosis due to the advanced disease stages by the time it is diagnosed, high recurrence rates and metastasis. In the present study, we investigated the effects of metformin (a safe anti-diabetic drug) and curcumin (a turmeric polyphenol extracted from rhizome of Curcuma longa Linn.) on proliferation, apopto...

Anoikis is a fundamental cellular process for maintaining tissue homeostasis. Resistance to anoikis is a hallmark of oncogenic epithelial–mesenchymal transition and is a pre-requisite for metastasis. Previous studies have revealed that the heavily glycosylated mucin protein MUC1, which is overexpressed in all types of epithelial cancer cells, preve...

Brought to you by the editorial team of Cell Death and Differentiation, Cell Death and Disease is a peer-reviewed author-pays online journal in the field of translational cell death. It seeks to promote diverse and integrated areas of Experimental and Internal Medicine with its specialties, including Cancer, Immunity and Neuroscience.

Sclerotium rolfsii lectin (SRL) is a lectin isolated from the fungus Sclerotium rolfsii and has exquisite binding specificity towards the oncofetal Thomsen-Friedenreich antigen (TF-Ag; Galβ1-3GalNAcα-O-Ser/Thr) and its derivatives. Previous studies have shown that SRL inhibits the proliferation of human colon, breast and ovarian cancer cells in vit...

Scope: Although the previous trials of inflammation have indicated that morin hydrate (MO) hold considerable promise, understanding the distinct mechanism of MO against inflammation remains a challenge. Methods and results: This study investigated the effect of MO in atherosclerosis in ApoE(-/-) mice and underlying cell signaling of MO effect in...

Aberrant glycosylation of cell membrane proteins is a universal feature of cancer cells. One of the most common glycosylation changes in epithelial cancer is the increased occurrence of the oncofetal Thomsen–Friedenreich disaccharide Galβ1–3GalNAc (T or TF antigen), which appears in about 90% of cancers but is rarely seen in normal epithelium. Over...

Background: TF antigen specific Sclerotium rolfsii lectin (SRL) inhibits human colon epithelial cancer HT29 cell growth by induction of apoptosis through cell surface binding and has tumor suppressing effect in vivo as reported earlier. Here we report the purification, identification and characterization of SRL binding membrane proteins from HT29 c...

Sclerotium rolfsii lectin (SRL) is a lectin isolated from fungus Sclerotium rolfsii and has high binding specificity towards the oncofetal Thomsen-Friedenreich carbohydrate antigen (Galβ1-3GalNAc-α-O-Ser/Thr, T or TF), which is expressed in more than 90% of human cancers. Our previous studies have shown that binding of SRL to human colon, breast an...

Concentrations of circulating galectin-3, a metastasis promoter, are greatly increased in cancer patients. Here we show that 2- or 6-de-O-sulfated, N-acetylated heparin derivatives are galectin-3 binding inhibitors. These chemically modified heparin derivatives inhibited galectin-3-ligand binding and abolished galectin-3-mediated cancer cell-endoth...

Sclerotium rolfsii lectin (SRL) isolated from the phytopathogenic fungus Sclerotium rolfsii has exquisite binding specificity towards O-linked, Thomsen-Freidenreich (Galβ1-3GalNAcα1-Ser/Thr, TF) associated glycans. This study investigated the influence of SRL on proliferation of human breast cancer cells (MCF-7 and ZR-75), non-tumorigenic breast ep...

Peanut agglutinin (PNA), which accounts for about 0.15% of the weight of the common peanut, is a carbohydrate-binding protein that binds the oncofetal Thomsen-Friedenreich disaccharide (galactoseβ1,3N-acetylgalactosamine-, TF) that is over-expressed by about 90% of human cancers. Previous studies have shown that PNA is highly resistant to cooking a...

Anoikis, a special apoptotic process occurring in response to loss of cell adhesion to the extracellular matrix, is a fundamental surveillance process for maintaining tissue homeostasis. Resistance to anoikis characterises cancer cells and is a pre-requisite for metastasis. This study shows that overexpression of the transmembrane mucin protein MUC...

Background: Circulating concentrations of the cytokines interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and chemokines monocyte chemotatic protein 1 (MCP-1)/CCL2 and growth-regulator oncogene α (GROα)/chemokine C-X-C motif ligand 1 are commonly increased in cancer patients and they are increasingly recognised as important promot...

We investigated the effects of CXC137, a tetramethylpyrazine piperazine derivate, on cell damage induced by N-methyl-D-aspartate (NMDA) in human derived neuroblastoma cells (SH-SY5Y) and its effect on memory dysfunction of rats with vascular dementia. It was found that the presence of CXC137 increased SH-SY5Y cells viability by inhibition of cell a...

It has long been presumed, though with surprisingly little evidence, a competition between Core 1 Gal-transferase (C1GalT), Core 3 GlcNAc-transferase (C3GnT) and sialyl-transferase (ST6GalNAc-T) for elongation of O-linked mucin-type glycans initiated with GalNAcα-Ser/Thr. This study tested this presumption by selective suppression of one of these g...

PTEN (Phosphatase and tensin homolog deleted on chromosome 10) is a tumor suppressor and has been suggested recently to be involved in the regulation of cardiovascular diseases. The molecular mechanisms of this regulation are however poorly understood. This study shows that down regulation of PTEN expression and activity by angiotensin II (Ang II)...

Elevated concentrations of several galectin members (e.g. galectin-2, -3, -4 and -8) occur in the bloodstream of patients with many types of cancers including colorectal, breast, bladder, head and neck, lung, pancreatic and melanoma. Patients with metastatic disease are also seen to have even higher levels of circulating galectins than those with o...

Background: Development of effective ways to detect metastases is highly desirable for improving the therapeutic strategies and survival of cancer patients. Serum levels of galectin-3 and -4, two members of the galactoside-binding galectin family, have recently been reported to be markedly increased up to 31-fold in the bloodstream of colorectal c...

Introduction Galectin-3 is a galactoside-binding protein whose concentration is increased up to 31-fold in the bloodstream of patients with cancer including colorectal cancer. We have recently shown that circulating galectin-3 promotes metastasis. This effect of galectin-3 is partly due to its interaction with the transmembrane mucin protein MUC1 e...

Glycan array analysis of Sclerotium rolfsii lectin (SRL) revealed its exquisite binding specificity to the oncofetal Thomsen-Friedenreich (Galβ1-3GalNAcα-O-Ser/Thr, T or TF) antigen and its derivatives. This study shows that SRL strongly inhibits the growth of human colon cancer HT29 and DLD-1 cells by binding to cell surface glycans and induction...

Galectin-3 is a mammalian β-galactoside-binding protein that is expressed by various types of human cells. Changes in galectin-3 expression and subcellular and intercellular localizations are commonly seen in cancer and pre-cancerous conditions. It is increasingly recognized that galectin-3 is an important regulator of a broad range of cancer cell...

Galectins constitute a family of 15 mammalian galactoside-binding proteins that share a consensus amino acid sequence in their carbohydrate binding sites. They are multi-functional molecules and are expressed widely in human tissues. Four galectins: galectin -1, -3, -4 and -8 are expressed in the human colon and rectum and their expressions show si...

Multidrug resistance (MDR) of tumor cells is a major obstacle in chemotherapeutic cancer treatment. Over-expression of glutathione S-transferase π (GSTπ) is one of the mechanisms contributing to MDR. In this study, we investigated the reversal of MDR by DLJ14, a ligustrazine derivate, in adriamycin (Adr) resistant human myelogenous leukemia (K562/A...

Sclerotium rolfsii lectin (SRL), a secretory protein from the soil borne phytopathogenic fungus Sclerotium rolfsii, has shown in our previous studies to bind strongly to the oncofetal Thomson-Friedenreich carbohydrate (Galβ1-3GalNAc-ser/thr, T or TF) antigen. TF antigen is widely expressed in many types of human cancers and the strong binding of SR...

Glycosylation is the process of attachment of sugar molecules , usually in chains (oligosaccharides), to proteins and lipids to form the glycoproteins and glycolipids found in eukaryotic and some prokaryotic organisms. The presence of oligosaccharides on a protein can have substantial effects on its size, stability, charge and antigenicity. The var...

Glycosylation, including O-linked, mucin type, has an import role in the function and activity of many proteins, particularly those that are secreted or transcellular. Previous studies have indicated that mucin-type O-linked glycans may also be carried by intra-cellular proteins such as the stress-related protein Orp150 that is involved in classica...

Increased concentrations of free circulating galectin-3 are commonly seen in the blood circulation of patients with many types of cancers including colorectal cancer. Recent studies have shown that changes in circulating galectin-3 levels in cancer patients may contribute significantly to the metastatic spread of disseminating cancer cells by enhan...

A tetramethylpyrazine analogue, CXC195, was synthesized by the Boekelheide reaction, in which the second methyl group of tetramethylpyrazine (TMP) was replaced with (4,4'-fluorine) diphenyl-methyl-1-piperazidine, the active group of flunarizine. We have observed protective effects of CXC195 on vascular endothelial cell survival under oxidative stre...

The organic anion-transporting polypeptides (rodents: Oatps; human: OATPs) belong to the growing family of organic anion/prostaglandin transporters and are important components of the active efflux transport system at the choroid plexus epithelial cells. OATPs facilitate the elimination of xenobiotics and endogenous waste from the cerebrospinal flu...

Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show in this study that galectin-3, the concentration of which is greatly increased in the circulation of cancer patients, increases cancer cell adhesion to macrovascular and microvascular endothelial cells under static and flow condition...

Similar changes in glycosylation occur in the colonic epithelium in inflammatory conditions such as ulcerative colitis and Crohn's disease and also in colon cancer and precancerous adenomatous polyps. They include reduced length of O-glycans, reduced sulfation, increased sialylation and increased expression of oncofetal carbohydrate antigens, such...

In this study, we investigated the effect of plagiochin E (PLE), a botanic-derived phenolic natural product, on reversal of fungal resistance to fluconazole (FLC) in vitro and the related mechanism. A synergistic action of PLE and FLC was observed in the FLC-resistant Candida albicans strains and was evaluated using the fractional inhibited concent...

The oncofetal Thomsen-Friedenreich carbohydrate antigen (Galbeta1-3GalNAcalpha1-Ser/Thr TF or T antigen) is a pan-carcinoma antigen highly expressed by about 90% of all human carcinomas. Its broad expression and high specificity in cancer have attracted many investigations into its potential use in cancer diagnosis and immunotherapy. Over the past...

Patients with metastatic cancer commonly have increased serum galectin-3 concentrations, but it is not known whether this has any functional implications for cancer progression. We report that MUC1, a large transmembrane mucin protein that is overexpressed and aberrantly glycosylated in epithelial cancer, is a natural ligand for galectin-3. Recombi...

Protein phosphatase 2A (PP2A) is a family of mammalian serine/threonine phosphatases that is involved in the control of many cellular functions including those mediated by extracellular signal-regulated kinase (ERK) signaling. While investigating the reversible antiproliferative effect of the dietary lectin, jacalin, which binds the Thomsen-Frieden...

The retinal pigment epithelium (RPE) plays a major role in the development of the anomalous retinal scarring response termed proliferative vitreoretinopathy. The present study was undertaken to investigate whether agaricus bisporus lectin inhibited human RPE proliferation in vitro. Fluorescein isothiocyanate-labeled agaricus bisporus lectin was use...