Galectins as Molecular Targets for Therapeutic Intervention

Dings, Ruud P.M.; Miller, Michelle C.; Griffin, Robert J.; Mayo, Kevin H.

doi:10.3390/ijms19030905

Cited by 93 publications

(101 citation statements)

References 180 publications

(241 reference statements)

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“…Abnormal expression of tumor-associated galectins correlates with the development, progression and clinical aggressiveness of the tumors, as well as the contribution to metastatic phenotype [54,[126][127][128][129][130][131]. Tumor-derived galectins have opposite functions on different immune cells that either promote inflammation or decrease immune responses, depending on the inflammatory environment among tumor cells.…”

Section: Gal-3 In Tumors and The Prognosismentioning

confidence: 99%

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Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

et al. 2020

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Galectin-3 is a β-galactoside-binding lectin which is important in numerous biological activities in various organs, including cell proliferation, apoptotic regulation, inflammation, fibrosis, and host defense. Galectin-3 is predominantly located in the cytoplasm and expressed on the cell surface, and then often secreted into biological fluids, like serum and urine. It is also released from injured cells and inflammatory cells under various pathological conditions. Many studies have revealed that galectin-3 plays an important role as a diagnostic or prognostic biomarker for certain types of heart disease, kidney disease, viral infection, autoimmune disease, neurodegenerative disorders, and tumor formation. In particular, it has been recognized that galectin-3 is extremely useful for detecting many of these diseases in their early stages. The purpose of this article is to review and summarize the recent literature focusing on the biomarker characteristics and long-term outcome predictions of galectin-3, in not only patients with various types of diseases, but associated animal models.

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Section: Gal-3 In Tumors and The Prognosismentioning

confidence: 99%

“…This means that the tumor-derived galectins have bipotential consequences on both tumor and immune cells [130]. Thus, new therapeutic strategies may be designed to facilitate the use of galectins as biological response modifiers to either tumor cells or immune cells [54,129,131].…”

Section: Gal-3 In Tumors and The Prognosismentioning

confidence: 99%

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

et al. 2020

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“…Mammalian Galectins comprise a family of 15 carbohydrate-binding proteins that are involved in many physiological functions, such as apoptosis, immune response, inflammation, angiogenesis, adhesion, and migration, as well as cell transformation and tumor growth [18]. All Galectin family members exhibit a conserved β-galactoside binding site within the common~130 aa carbohydrate recognition domains (CRDs) for carbohydrate-dependent interactions with extracellular glycoconjugates.…”

Section: Introductionmentioning

confidence: 99%

Galectin-8 binds to the Farnesylated C-terminus of K-Ras4B and Modifies Ras/ERK Signaling and Migration in Pancreatic and Lung Carcinoma Cells

Meinohl

Barnard

Fritz‐Wolf

et al. 2019

Cancers

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K-Ras is the most prominent driver of oncogenesis and no effective K-Ras inhibitors have been established despite decades of intensive research. Identifying new K-Ras-binding proteins and their interaction domains offers the opportunity for defining new approaches in tackling oncogenic K-Ras. We have identified Galectin-8 as a novel, direct binding protein for K-Ras4B by mass spectrometry analyses and protein interaction studies. Galectin-8 is a tandem-repeat Galectin and it is widely expressed in lung and pancreatic carcinoma cells. siRNA-mediated depletion of Galectin-8 resulted in increased K-Ras4B content and ERK1/2 activity in lung and pancreatic carcinoma cells. Moreover, cell migration and cell proliferation were inhibited by the depletion of Galectin-8. The K-Ras4B–Galectin-8 interaction is indispensably associated with the farnesylation of K-Ras4B. The lysine-rich polybasic domain (PBD), a region that is unique for K-Ras4B as compared to H- and N-Ras, stabilizes the interaction and accounts for the specificity. Binding assays with the deletion mutants of Galectin-8, comprising either of the two carbohydrate recognition domains (CRD), revealed that K-Ras4B only interacts with the N-CRD, but not with the C-CRD. Structural modeling uncovers a potential binding pocket for the hydrophobic farnesyl chain of K-Ras4B and a cluster of negatively charged amino acids for interaction with the positively charged lysine residues in the N-CRD. Our results demonstrate that Galectin-8 is a new binding partner for K-Ras4B and it interacts via the N-CRD with the farnesylated PBD of K-Ras, thereby modulating the K-Ras effector pathways as well as cell proliferation and migration.

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“…In conclusion, the present study characterizes the capacity of the human Gal3 lectin to bind non-classical anti-cancer compounds [42], in particular Au 3+ TPPS that appears to be an appropriate alternative to classical anti-cancer compounds [52][53][54][55][56], and reveals new perspectives in the drug delivery of anti-cancer agents [62].…”

Section: Discussionmentioning

confidence: 85%

Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3

et al. 2019

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Gold(III) porphyrin presents an attractive alternative to the use of, for example, cisplatin in chemotherapy. However, approaches that allow to selectively target cancer cells are highly sought. Many plant and mammalian lectins have been shown to bind oligosaccharide sequences of the aberrant glycosylation pattern found on cancerous tumors. For example human galectin-3, of the galectin family specific for β-galactoside, is overexpressed in the extracellular matrix of tumorigenous and metastatic tissues. We searched for non-carbohydrate ligands for galectin-3 that can guide a cytotoxic drug to the cancer cells by maintaining its affinity for tumor associated carbohydrate antigens. Previous findings showed that zinc tetrasulfonatophenylporphyrin can bind galectin-3 with sub-micromolar affinity without disturbing lactose binding. Gold(III) porphyrin is not only cytotoxic to cancer cells, it knows also a potential application as photosensitiser in photodynamic therapy. We investigated the binding of gold(III) porphyrin to galectin-3 using different biophysical interaction techniques and demonstrated a low micromolar affinity of human galectin-3 for the cytotoxic compound. Co-crystallization attempts in order to understand the binding mode of gold porphyrin to galectin-3 failed, but molecular docking emphasized a highly populated secondary binding site that does not hinder lactose or Thomsen Friendenreich disaccharide binding. This suggests that gold(III) porphyrin might significantly enhance its concentration and delivery to cancer cells by binding to human galectin-3 that keeps its orientation towards tumor associated carbohydrate antigens.

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Galectins as Molecular Targets for Therapeutic Intervention

Cited by 93 publications

References 180 publications

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

Galectin-3 as a Next-Generation Biomarker for Detecting Early Stage of Various Diseases

Galectin-8 binds to the Farnesylated C-terminus of K-Ras4B and Modifies Ras/ERK Signaling and Migration in Pancreatic and Lung Carcinoma Cells

Binding of Gold(III) Porphyrin by the Pro-metastatic Regulatory Protein Human Galectin-3

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