Characterization of<i>LGALS3</i>(galectin-3) as a player in DNA damage response

Carvalho, Renato S.; Fernandes, Vanessa C.; Nepomuceno, Thales C.; Rodrigues, Deivid C.; Woods, Nicholas T.; Suarez‐Kurtz, Guilherme; Chammas, Roger; Monteiro, Alvaro N.A.; Carvalho, Marcelo A.

doi:10.4161/cbt.28873

Cited by 27 publications

(23 citation statements)

References 57 publications

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“…Despite the absence of glycan ligands in intracellular compartment, electrostatic potential calculations show a linear array of three positively charged arginine residues in a cleft of galectin-3 CRD that suggests a possible binding site to RNA ( 23 ). In the same context, intracellular galectin-3 CRD modulates DNA damage response through interacting with BARD1, a BRCA1 partner ( 50 ), and attenuates the pro-apoptotic activity of Bax through interaction with members of the bcl-2 family ( 51 – 55 ).…”

Section: Galectin-3 and Its Key Structure To Function Relationshipsmentioning

confidence: 99%

Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments

et al. 2016

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Galectin-3 is a member of the β-galactoside-binding lectin family, whose expression is often dysregulated in cancers. While galectin-3 is usually an intracellular protein found in the nucleus and in the cytoplasm, under certain conditions, galectin-3 can be secreted by an yet unknown mechanism. Under stressing conditions (e.g., hypoxia and nutrient deprivation) galectin-3 is upregulated, through the activity of transcription factors, such as HIF-1α and NF-κB. Here, we review evidence that indicates a positive role for galectin-3 in MAPK family signal transduction, leading to cell proliferation and cell survival. Galectin-3 serves as a scaffold protein, which favors the spatial organization of signaling proteins as K-RAS. Upon secretion, extracellular galectin-3 interacts with a variety of cell surface glycoproteins, such as growth factor receptors, integrins, cadherins, and members of the Notch family, among other glycoproteins, besides different extracellular matrix molecules. Through its ability to oligomerize, galectin-3 forms lectin lattices that act as scaffolds that sustain the spatial organization of signaling receptors on the cell surface, dictating its maintenance on the plasma membrane or their endocytosis. Galectin-3 induces tumor cell, endothelial cell, and leukocyte migration, favoring either the exit of tumor cells from a stressed microenvironment or the entry of endothelial cells and leukocytes, such as monocytes/macrophages into the tumor organoid. Therefore, galectin-3 plays homeostatic roles in tumors, as (i) it favors tumor cell adaptation for survival in stressed conditions; (ii) upon secretion, galectin-3 induces tumor cell detachment and migration; and (iii) it attracts monocyte/macrophage and endothelial cells to the tumor mass, inducing both directly and indirectly the process of angiogenesis. The two latter activities are potentially targetable, and specific interventions may be designed to counteract the protumoral role of extracellular galectin-3.

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Section: Galectin-3 and Its Key Structure To Function Relationshipsmentioning

confidence: 99%

Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments

et al. 2016

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“…Silencing galectin-3 in HeLa cells has resulted in the increased resistance of transfected cells to DNA-damaging agents, such as ionizing radiation (10-40 Gy), etoposide, carboplatin, and mitomycin C [115]. Galectin-3 protein levels in glioblastoma cells increased in response to UV-C radiation and treatments with alkylating reagents, and required the involvement of such transcription factors as NF-jB and Jun [116].…”

Section: Chimeric Type Galectin-3mentioning

confidence: 99%

Towards molecular mechanisms regulating the expression of galectins in cancer cells under microenvironmental stress conditions

Timoshenko

2015

Cell. Mol. Life Sci.

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Galectins, a family of soluble β-galactoside-binding proteins, serve as mediators of fundamental biological processes, such as cell growth, differentiation, adhesion, migration, survival, and death. The purpose of this review is to summarize the current knowledge regarding the ways in which the expression of individual galectins differs in normal and transformed human cells exposed to various stimuli mimicking physiological and pathological microenvironmental stress conditions. A conceptual point is being made and grounded that the modulation of galectin expression profiles is a key aspect of cellular stress responses. Moreover, this modulation might be precisely regulated at transcriptional and post-transcriptional levels in the context of non-overlapping transcription factors and miRNAs specific to galectins.

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“…( b ) SR proteins and two members of the galectin family, galectin-1 and galectin-3, are expressed in the nucleus and involved in pre-mRNA splicing. However, SR proteins and galectin-3 share some other striking features, such as shuttling between the nucleus and cytoplasm and involvement in genome stability [ 120 , 122 , 123 , 124 , 125 , 126 ]. The RBP role of galectin-3 is mediated through the hnRNPL interaction, as shown by Coppin et al [ 120 ].…”

Section: Figurementioning

confidence: 99%

“…Galectin-3 is involved in the mRNA life-cycle through different ways: through binding with the ribonucleoprotein U1 of the spliceosome [ 131 , 132 ], through stabilizing mRNA (through hnRNP-L interaction), and through mRNA nuclear export and storage in cytoplasmic granules [ 120 ]. Galectin-3 also acts as a player in the DNA damage response through its interaction with BARD1 in a large complex involving a BRCA1/BARD1 heterodimer [ 126 ]. Galectin-3 interacts in an O-GlcNAcylation-dependent manner with a key mitotic regulator, the nuclear mitotic apparatus protein (NuMA), which is required for the establishment and the cohesion of the mitotic spindle [ 125 ].…”

Section: Figurementioning

confidence: 99%

Messenger RNA Life-Cycle in Cancer Cells: Emerging Role of Conventional and Non-Conventional RNA-Binding Proteins?

Coppin

Leclerc

Vincent

et al. 2018

IJMS

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Functional specialization of cells and tissues in metazoans require specific gene expression patterns. Biological processes, thus, need precise temporal and spatial coordination of gene activity. Regulation of the fate of messenger RNA plays a crucial role in this context. In the present review, the current knowledge related to the role of RNA-binding proteins in the whole mRNA life-cycle is summarized. This field opens up a new angle for understanding the importance of the post-transcriptional control of gene expression in cancer cells. The emerging role of non-classic RNA-binding proteins is highlighted. The goal of this review is to encourage readers to view, through the mRNA life-cycle, novel aspects of the molecular basis of cancer and the potential to develop RNA-based therapies.

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Characterization ofLGALS3(galectin-3) as a player in DNA damage response

Cited by 27 publications

References 57 publications

Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments

Galectin-3 Determines Tumor Cell Adaptive Strategies in Stressed Tumor Microenvironments

Towards molecular mechanisms regulating the expression of galectins in cancer cells under microenvironmental stress conditions

Messenger RNA Life-Cycle in Cancer Cells: Emerging Role of Conventional and Non-Conventional RNA-Binding Proteins?

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