Overexpression of galectin‐1 is associated with poor prognosis in human hepatocellular carcinoma following resection

Wu, Han; Chen, Pei; Liao, Rui; Li, Yiwei; Yi, Yong; Wang, Jiaxing; Sun, Tai-Wei; Zhou, Jian; Shi, Ying‐Hong; Yang, Xin‐Rong; Jia, Jianjun; Cheng, Yunfeng; Fan, Jia; Qiu, Shuang–Jian

doi:10.1111/j.1440-1746.2012.07130.x

Cited by 54 publications

(52 citation statements)

References 34 publications

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“…We also showed that a high serum galectin-1 level was an independent factor associated with poor progress-free survival and overall survival. Additionally, HCC tissue microarray analysis showed that patients with high galectin-1 expression had a higher rate of tumor recurrence and shorter overall survival than those with lower galectin-1 expression (45). Taken together, these data may suggest that the serum levels of galectin-1 can serve as a prognostic factor for HCC.…”

Section: Discussionmentioning

confidence: 77%

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Yeh¹,

Hsu

Shao

et al. 2015

Molecular & Cellular Proteomics

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Sorafenib has become the standard therapy for patients with advanced hepatocellular carcinoma (HCC). Unfortunately, most patients eventually develop acquired resistance. Therefore, it is important to identify potential biomarkers that could predict the efficacy of sorafenib. To identify target proteins associated with the development of sorafenib resistance, we applied stable isotope labelling with amino acids in cell culture (SILAC)-based quantitative proteomic approach to analyze differences in protein expression levels between parental HuH-7 and sorafenib-acquired resistance HuH-7 (HuH-7 R ) cells in vitro, combined with an isobaric tags for relative and absolute quantitation (iTRAQ) quantitative analysis of HuH-7 and HuH-7 R tumors in vivo. In total, 2,450 quantified proteins were identified in common in SILAC and iTRAQ experiments, with 81 showing increased expression (>2.0-fold) with sorafenib resistance and 75 showing decreased expression (<0.5-fold). In silico analyses of these differentially expressed proteins predicted that 10 proteins were related to cancer with involvements in cell adhesion, migration, and invasion. Knockdown of one of these candidate proteins, galectin-1, decreased cell proliferation and metastasis in HuH-7 R cells and restored sensitivity to sorafenib. We verified galectin-1 as a predictive marker of sorafenib resistance and a downstream target of the AKT/mTOR/HIF-1␣ signaling pathway. In addition, increased galectin-1 expression in HCC patients' serum was associated with poor tumor control and low response rate. We also found that a high serum galectin-1 level was an independent factor associated with poor progression-free survival and overall survival. In conclusion, these results suggest that galectin-1 is a possible biomarker for predicting the response of HCC patients to treatment with sorafenib. As such, it may assist in the stratification of HCC and help direct personalized therapy. Molecular & Cellular

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Section: Discussionmentioning

confidence: 77%

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Yeh¹,

Hsu

Shao

et al. 2015

Molecular & Cellular Proteomics

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“…Expression of Gal1 is associated with the aggressiveness of hepatocellular carcinoma (HCC) in mice [11], low survival of HCC patients [12], and poor prognosis in HCC following resection [13]. Interestingly, Gal1 acts by promoting HCC cell adhesion through PI3K and/or ERK1/2 signaling pathways [14].…”

Section: Introductionmentioning

confidence: 99%

Galectin-1 is essential for efficient liver regeneration following hepatectomy

et al. 2016

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Galectin-1 (Gal1) is a known immune/inflammatory regulator which acts both extracellularly and intracellularly, modulating innate and adaptive immune responses. Here, we explored the role of Gal1 in liver regeneration using 70% partial hepatectomy (PHx) of C57BL/6 wild type and Gal1-knockout (Gal1-KO, Lgals1−/−) mice. Gene or protein expression, in liver samples collected at time intervals from 2 to 168 hours post-operation, was tested by either RT-PCR or by immunoblotting and immunohistochemistry, respectively. We demonstrated that Gal1 transcript and protein expression was induced in the liver tissue of wild type mice upon PHx. Liver regeneration following PHx was significantly delayed in the Gal1-KO compared to the control liver. This delay was accompanied by a decreased Akt phosphorylation, and accumulation of the hepatocyte nuclear p21 protein in the Gal1-KO versus control livers at 24 and 48 hours following PHx. Transcripts of several known regulators of inflammation, cell cycle and cell signaling, including some known PHx-induced genes, were aberrantly expressed (mainly down-regulated) in Gal1-KO compared to control livers at 2, 6 and 24 hours post-PHx. Transient steatosis, which is imperative for liver regeneration following PHx, was significantly delayed and decreased in the Gal1-KO compared to the control liver and was accompanied by a significantly decreased expression in the mutant liver of several genes encoding lipid metabolism regulators. Our results demonstrate that Gal1 protein is essential for efficient liver regeneration following PHx through the regulation of liver inflammation, hepatic cell proliferation, and the control of lipid storage in the regenerating liver.

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“…Increased gal-1 expression is detected in primary human prostate, colorectal, bladder, pancreatic, liver, thyroid, ovarian, uterine, cervical, and brain cancers, where its expression is correlated with worse histological grade and poor patient prognosis (5–14). Since it was first shown that cell surface gal-1 induces apoptosis in cytotoxic T-cells (15), it has been proposed that this represents the sole mechanism by which tumor-derived gal-1 suppresses anti-tumor immunity (16–21).…”

Section: Introductionmentioning

confidence: 99%

Natural Killer Cells Eradicate Galectin-1–Deficient Glioma in the Absence of Adaptive Immunity

et al. 2014

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Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immune surveillance. However, the immune escape mechanisms used by malignant brain tumors to subvert this innate type of immune surveillance remain unclear. Here we show that malignant glioma cells suppress NK immune surveillance by overexpressing the β-galactoside-binding lectin galectin-1. Conversely, galectin-1 deficient glioma cells could be eradicated by host NK cells prior to the initiation of an anti-tumor T-cell response. In vitro experiments demonstrated that galectin-1 deficient GL26-Cit glioma cells are ~3-fold more sensitive to NK-mediated tumor lysis that galectin-1 expressing cells. Our findings suggest that galectin-1 suppression in human glioma could improve patient survival by restoring NK immune surveillance that can eradicate glioma cells.

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Overexpression of galectin‐1 is associated with poor prognosis in human hepatocellular carcinoma following resection

Abstract: Galectin-1 might be a new prognostic factor for HCC after resection and could potentially be a high-priority therapeutic target.

Cited by 54 publications

References 34 publications

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Integrated Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) and Isobaric Tags for Relative and Absolute Quantitation (iTRAQ) Quantitative Proteomic Analysis Identifies Galectin-1 as a Potential Biomarker for Predicting Sorafenib Resistance in Liver Cancer*

Galectin-1 is essential for efficient liver regeneration following hepatectomy

Natural Killer Cells Eradicate Galectin-1–Deficient Glioma in the Absence of Adaptive Immunity

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