Silencing of galectin-3 represses osteosarcoma cell migration and invasion through inhibition of FAK/Src/Lyn activation and β-catenin expression and increases susceptibility to chemotherapeutic agents

Park, Ga Bin; Kim, Dae‐Jin; Kim, Yeong-Seok; Lee, Hyun-Kyung; Kim, Chang-Wan; Hur, Dae Young

doi:10.3892/ijo.2014.2721

Cited by 50 publications

(47 citation statements)

References 42 publications

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“…7A and B). These results are consistent with reported conclusions that Gal3C could induce Erk phosphorylation in HeLa cells 70 , and Galectin-3 is important for FAK/SRC signalling transduction 71 . The FAK/SRC pathway is always abnormally activated in HCC, and it contributes to invasion and metastasis, leading to poor survival 5–8 .…”

Section: Discussionsupporting

confidence: 93%

Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate recognition domain of Galectin-3 in Hepatocellular carcinoma

Wang

Tian

Ying

et al. 2017

Sci Rep

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Hepatocellular carcinoma (HCC) is a serious threat to human health. The carbohydrate recognition domain of Galectin-3 (Gal3C) has been reported to be an anti-tumour molecule. In this study, we aim to explore effects of Gal3C in HCC and its possible molecular mechanism with quantitative proteomics approach. We found that rGal3C stimulation could inhibit cell viability, migration and invasion of HepG2. After rGal3C stimulating, 190 proteins were differentially expressed. Eighty up-regulated proteins located mainly in extracellular exosome and involved in cell adhesion and metabolism, and 110 down-regulated proteins located in mitochondria and extracellular exosome, and related to processes of metabolism and oxidation-reduction. Of the differentially expressed proteins, CLU, NDRG1, CD166, S100A11 and Galectin-1 were carcinoma-related proteins affected by rGal3C. Potential receptors of rGal3C were explored by an UV cross-linking capture strategy. We showed that rGal3C could induce dephosphorylating of FAK/SRC. Blocking of the FAK/SRC pathway resulted in down-regulation of NDRG1. Immunofluorescence suggested that rGal3C could disrupt integrin clustering. Our study provides valuable insight into the anti-tumour mechanism of rGal3C in HCC on a proteomics level and is the first to reveal the possible mechanism involving integrin/FAK/SRC pathway and NDRG1. These results provide useful guidance of developing new therapies for HCC.

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Section: Discussionsupporting

confidence: 93%

Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate recognition domain of Galectin-3 in Hepatocellular carcinoma

Wang

Tian

Ying

et al. 2017

Sci Rep

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“…The former is an upstream target of the IL-6 signaling pathway; its downregulation proves efficient IL-6 inhibition and possibility contributes to a blockade in cell proliferation [60]. The latter promotes β-catenin/Wnt signaling, and β-catenin-related oncogenesis has been frequently reported in osteosarcoma; its silencing is associated with inhibited secretion of IL-6 [61]. Overall, we show that the vicinity to stromal cells increases the expression of adhesion molecules and that IL-6 contributes to their overexpression.…”

Section: Discussionmentioning

confidence: 99%

Tumor-Activated Mesenchymal Stromal Cells Promote Osteosarcoma Stemness and Migratory Potential via IL-6 Secretion

et al. 2016

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Osteosarcoma (OS) is an aggressive bone malignancy with a high relapse rate despite combined treatment with surgery and multiagent chemotherapy. As for other cancers, OS-associated microenvironment may contribute to tumor initiation, growth, and metastasis. We consider mesenchymal stromal cells (MSC) as a relevant cellular component of OS microenvironment, and have previously found that the interaction between MSC and tumor cells is bidirectional: tumor cells can modulate their peripheral environment that in turn becomes more favorable to tumor growth through metabolic reprogramming. Here, we determined the effects of MSC on OS stemness and migration, two major features associated with recurrence and chemoresistance. The presence of stromal cells enhanced the number of floating spheres enriched in cancer stem cells (CSC) of the OS cell population. Furthermore, the co-culturing with MSC stimulated the migratory capacity of OS via TGFβ1 and IL-6 secretion, and the neutralizing antibody anti-IL-6 impaired this effect. Thus, stromal cells in combination with OS spheres exploit a vicious cycle where the presence of CSC stimulates mesenchymal cytokine secretion, which in turn increases stemness, proliferation, migration, and metastatic potential of CSC, also through the increase of expression of adhesion molecules like ICAM-1. Altogether, our data corroborate the concept that a comprehensive knowledge of the interplay between tumor and stroma that also includes the stem-like fraction of tumor cells is needed to develop novel and effective anti-cancer therapies.

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“…As reported previously, FAK/Src/Lyn activation and b-catenin expression stimulated by Gal-3 knockdown also contribute to osteosarcoma cell migration and invasion. 31 RhoA and Myosin light-chain kinase activation were reported to regulate the effect of Gal-3 in hepatocellular carcinoma. 32 Gal-3 also plays important roles in apoptosis.…”

mentioning

confidence: 99%

Antitumor effects of galectin-3 inhibition in human renal carcinoma cells

Sun

et al. 2016

Exp Biol Med (Maywood)

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Galectins are thought to be prognosticators for survival in renal cell cancer. However, the biological activity of galectin-3 (Gal-3) in renal carcinoma cells is still debated. In this study, immunohistochemical staining confirmed a high expression of Gal-3 in tumor tissue from renal cell carcinoma. Critically, Gal-3 expression was related to tumor cell differentiation. Consistent with Gal-3 expression in renal cell cancer, strong expression of Gal-3 was also observed in several renal tumor cell lines but not in normal renal cells. A Gal-3 high-expression cell line Caki-1 was chosen to study the biological activity of Gal-3. Using short hairpin RNA method, Gal-3 expression in Caki-1 cells was knocked down. We evidenced that Gal-3 knockdown inhibited cell proliferation and invasion, induced Caspase-3-dependent apoptosis and arrested cell cycle at G1 phase. Mechanically, Cyclin D1 expression decreased, but p27 increased after Gal-3 knockdown. Taken together, these results suggest that Gal-3 is related to the development of renal cell cancer and could serve as a target to therapy renal cell cancer.

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Silencing of galectin-3 represses osteosarcoma cell migration and invasion through inhibition of FAK/Src/Lyn activation and β-catenin expression and increases susceptibility to chemotherapeutic agents

Cited by 50 publications

References 42 publications

Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate recognition domain of Galectin-3 in Hepatocellular carcinoma

Quantitative proteomics reveal the anti-tumour mechanism of the carbohydrate recognition domain of Galectin-3 in Hepatocellular carcinoma

Tumor-Activated Mesenchymal Stromal Cells Promote Osteosarcoma Stemness and Migratory Potential via IL-6 Secretion

Antitumor effects of galectin-3 inhibition in human renal carcinoma cells

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