Galectin-3 Contributes to Melanoma Growth and Metastasis via Regulation of NFAT1 and Autotaxin

Braeuer, Russell R.; Zigler, Maya; Kamiya, Takafumi; Dobroff, Andrey S.; Huang, Li; Choi, Woonyoung; McConkey, David J.; Shoshan, Einav; Mobley, Aaron K.; Song, Renduo; Raz, Avraham; Bar‐Eli, Menashe

doi:10.1158/0008-5472.can-12-2424

Cited by 85 publications

(69 citation statements)

References 46 publications

(60 reference statements)

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“…In our study, we found that VEGF-C largely lost its ability to promote SiHa cell invasion when Gal-3 expression was silenced, suggesting a crucial role of Gal-3 in VEGF-C-promoted cervical cancer cell invasiveness. This is consistent with other studies showing that Gal-3 overexpression is associated with increased invasiveness of melanoma, ovarian, thyroid and colorectal cancer cells [12][13][14][15].…”

Section: Discussionsupporting

confidence: 93%

Vascular endothelial growth factor C enhances cervical cancer cell invasiveness via upregulation of galectin-3 protein

Liu

Cheng

et al. 2014

Gynecological Endocrinology

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Vascular endothelial growth factor C (VEGF-C) promotes cervical cancer metastasis, while the detailed mechanism remains obscure. Recent evidence shows that galectin-3 (Gal-3), a glycan binding protein, interacts with the VEGF receptors and reinforces their signal transduction. In this study, we investigated the role of Gal-3 in VEGF-C-induced cervical cancer cell invasion. On cervical carcinoma cell line SiHa cells, silencing of Gal-3 expression with specific siRNA largely impaired VEGF-C-enhanced cell invasion. Treatment with VEGF-C for 12-48 h enhanced Gal-3 protein expression, which was inhibited by the addition of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC). Moreover, the silencing of NF-κB subunit p65 expression with specific siRNA attenuated VEGF-C-enhanced Gal-3 expression, suggesting that NF-κB is the key intermediate. Under VEGF-C stimulation, an enhanced interaction between VEGF receptor-3 (VEGF-R3) and Gal-3 was found, which may possibly lead to VEGF-R3 activation since exogenous Gal-3 induced VEGF-R3 phosphorylation in a dose- and time-dependent manner. In conclusion, our findings implied that VEGF-C enhanced cervical cancer invasiveness via upregulation of Gal-3 protein through NF-κB pathway, which may shed light on potential therapeutic strategies for cervical cancer therapy.

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Section: Discussionsupporting

confidence: 93%

Vascular endothelial growth factor C enhances cervical cancer cell invasiveness via upregulation of galectin-3 protein

Liu

Cheng

et al. 2014

Gynecological Endocrinology

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“…Inhibition of galectin expression, using siRNA or antisense sequences, showed significant results in colon [233], ovarian [234], esophageal [235], hepatocarcinoma [236], glioma [237], glioblastoma [238], and melanoma [239] cell lines. Anti-galectin mAbs and Gal-3 recombinant were also effective in vitro studies with diverse cell lines [240-242].…”

Section: Discussionmentioning

confidence: 99%

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Silva-filho¹,

Sena²,

Lima

et al. 2017

Cell Physiol Biochem

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Post-translational and co-translational enzymatic addition of glycans (glycosylation) to proteins, lipids, and other carbohydrates, is a powerful regulator of the molecular machinery involved in cell cycle, adhesion, invasion, and signal transduction, and is usually seen in both in vivo and in vitro cancer models. Glycosyltransferases can alter the glycosylation pattern of normal cells, subsequently leading to the establishment and progression of several diseases, including cancer. Furthermore, a growing amount of research has shown that different oxygen tensions, mainly hypoxia, leads to a markedly altered glycosylation, resulting in altered glycan-receptor interactions. Alteration of intracellular glucose metabolism, from aerobic cellular respiration to anaerobic glycolysis, inhibition of integrin 3α1β translocation to the plasma membrane, decreased 1,2-fucosylation of cell-surface glycans, and galectin overexpression are some consequences of the hypoxic tumor microenvironment. Additionally, increased expression of gangliosides carrying N-glycolyl sialic acid can also be significantly affected by hypoxia. For all these reasons, it is possible to realize that hypoxia strongly alters glycobiologic events within tumors, leading to changes in their behavior. This review aims to analyze the complexity and importance of glycoconjugates and their molecular interaction network in the hypoxic context of many solid tumors.

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“…Specifically, galectin-3 reduces glioma cell migration (121). In general, however, galectin-3 (107) is mostly associated with increased invasive behavior in most cancer cell types tested (94,95,117,(122)(123)(124)(125)(126), supporting the view that targeting this galectin might be a promising avenue for the treatment of many types of cancer. Whether this is also true for other galectins has to be determined.…”

Section: Galectin (%) Cellular --------------------------------------mentioning

confidence: 95%

Intracellular galectins in cancer cells: Potential new targets for therapy

Vladoiu

Labrie

St‐Pierre

2014

International Journal of Oncology

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Abstract. Dysregulation of galectin expression is frequently observed in cancer tissues. Such an abnormal expression pattern often correlates with aggressiveness and relapse in many types of cancer. Because galectins have the ability to modulate functions that are important for cell survival, migration and metastasis, they also represent attractive targets for cancer therapy. This has been well-exploited for extracellular galectins, which bind glycoconjugates expressed on the surface of cancer cells. Although the existence of intracellular functions of galectins has been known for many years, an increasing number of studies indicate that these proteins can also alter tumor progression through their interaction with intracellular ligands. In fact, in some instances, the interactions of galectins with their intracellular ligands seem to occur independently of their carbohydrate recognition domain. Such findings call for a change in the basic assumptions, or paradigms, concerning the activity of galectins in cancer and may force us to revisit our strategies to develop galectin antagonists for the treatment of cancer.

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Galectin-3 Contributes to Melanoma Growth and Metastasis via Regulation of NFAT1 and Autotaxin

Cited by 85 publications

References 46 publications

Vascular endothelial growth factor C enhances cervical cancer cell invasiveness via upregulation of galectin-3 protein

Vascular endothelial growth factor C enhances cervical cancer cell invasiveness via upregulation of galectin-3 protein

Glycobiology Modifications in Intratumoral Hypoxia: The Breathless Side of Glycans Interaction

Intracellular galectins in cancer cells: Potential new targets for therapy

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