Galectin-3 favours tumour metastasis via the activation of β-catenin signalling in hepatocellular carcinoma

Song, Mengjia; Pan, Qiuzhong; Yang, Jin-Hao; He, Junyi; Zeng, Jianxiong; Cheng, Shaoyan; Huang, Yue; Zhou, Ziqi; Zhu, Qian; Yang, Chih Ping; Han, Yu; Tang, Yan; Chen, Hao; Weng, Desheng; Xia, Jianchuan

doi:10.1038/s41416-020-1022-4

Cited by 63 publications

(50 citation statements)

References 44 publications

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“…LGALS3 plays a signi cant role in the progression and metastasis of colon cancer, acute myeloid leukemia, melanoma, and pituitary tumors [40][41][42][43]. In addition, LGALS3 enhances HCC cell tumorigenesis and metastasis through the β-catenin signaling [44]. A series of studies have demonstrated that Galectin-3 can severe as a biomarker for prognosis predicting of HCC patients which are the same as our results [45][46][47].…”

Section: Discussionsupporting

confidence: 88%

A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

Liu

Wang

Zhang

et al. 2021

Preprint

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Background: Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated. Methods: To screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database(https://cancergenome.nih.gov/) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan-Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model. Results: Compared to normal tissues, 43 highly up-regulated and 8 down-regulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated two-year or five-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram. Conclusion: Based on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients.

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Section: Discussionsupporting

confidence: 88%

A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

Liu

Wang

Zhang

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…LGALS3 plays a significant role in the progression and metastasis of colon cancer, acute myeloid leukemia, melanoma, and pituitary tumors [ 40 – 43 ]. In addition, LGALS3 enhances HCC cell tumorigenesis and metastasis through the β-catenin signaling [ 44 ]. A series of studies have demonstrated that Galectin-3 can severe as a biomarker for prognosis predicting of HCC patients which are the same as our results [ 45 – 47 ].…”

Section: Discussionmentioning

confidence: 99%

A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

et al. 2021

View full text Add to dashboard Cite

Background Dysregulation of the balance between proliferation and apoptosis is the basis for human hepatocarcinogenesis. In many malignant tumors, such as hepatocellular carcinoma (HCC), there is a correlation between apoptotic dysregulation and poor prognosis. However, the prognostic values of apoptosis-related genes (ARGs) in HCC have not been elucidated. Methods To screen for differentially expressed ARGs, the expression levels of 161 ARGs from The Cancer Genome Atlas (TCGA) database (https://cancergenome.nih.gov/) were analyzed. Gene Ontology (GO) enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to evaluate the underlying molecular mechanisms of differentially expressed ARGs in HCC. The prognostic values of ARGs were established using Cox regression, and subsequently, a prognostic risk model for scoring patients was developed. Kaplan–Meier (K-M) and receiver operating characteristic (ROC) curves were plotted to determine the prognostic value of the model. Results Compared with normal tissues, 43 highly upregulated and 8 downregulated ARGs in HCC tissues were screened. GO analysis results revealed that these 51 genes are indeed related to the apoptosis function. KEGG analysis revealed that these 51 genes were correlated with MAPK, P53, TNF, and PI3K-AKT signaling pathways, while Cox regression revealed that 5 ARGs (PPP2R5B, SQSTM1, TOP2A, BMF, and LGALS3) were associated with prognosis and were, therefore, obtained to develop the prognostic model. Based on the median risk scores, patients were categorized into high-risk and low-risk groups. Patients in the low-risk groups exhibited significantly elevated 2-year or 5-year survival probabilities (p < 0.0001). The risk model had a better clinical potency than the other clinical characteristics, with the area under the ROC curve (AUC = 0.741). The prognosis of HCC patients was established from a plotted nomogram. Conclusion Based on the differential expression of ARGs, we established a novel risk model for predicting HCC prognosis. This model can also be used to inform the individualized treatment of HCC patients.

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“…Consistently, we found that β -catenin expression was decreased in parallel to the attenuation of AKT phosphorylation. In hepatocellular carcinoma, galectin-3 overexpression enhanced metastasis through the PI3K/AKT/GSK-3 β / β -catenin signaling cascade [ 33 ]. Our findings are further supported by a study demonstrating that β -catenin activation was highly dependent on the PI3K/AKT activity but not on the MAPK [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells

Lee

Hsu

et al. 2021

International Journal of Endocrinology

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Accumulating evidence suggests that galectin-3 is a histologic marker of thyroid cancer. However, the pharmacological lectin-based approach has not been well studied. In the present study, we aimed to investigate the therapeutic potential of novel galectin-3 inhibitors by treating thyroid cancer cells with different concentrations of GB1107 or TD139. At high doses, TD139, but not GB1107, reduced cell viability and clonogenicity of thyroid cancer cells. TD139 induced apoptosis of thyroid cancer cells, as evident by an increase in the percentage of sub-G1 cells on cell cycle analysis, caspase-3 activation, and PARP1 cleavage. Either GB1107 or TD139 significantly inhibited cell coherence and counteracted anoikis resistance. Both inhibitors decreased migratory and invasive abilities in a dose-dependent manner. Furthermore, GB1107 and TD139 treatment attenuated AKT phosphorylation and decreased the expression of β-catenin and MMP2. In conclusion, these novel galectin-3 inhibitors suppressed the anoikis resistance, motility, and invasive capacity of thyroid cancer cells at least partly through the AKT/β-catenin pathway. Galectin-3 inhibitors are potentially suitable for preclinical evaluation of treatment and/or prevention of metastatic spread in thyroid cancer.

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Galectin-3 favours tumour metastasis via the activation of β-catenin signalling in hepatocellular carcinoma

Cited by 63 publications

References 44 publications

A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

A prognostic model for hepatocellular carcinoma based on apoptosis-related genes

Galectin-3 Inhibitors Suppress Anoikis Resistance and Invasive Capacity in Thyroid Cancer Cells

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