Unraveling galectin-1 as a novel therapeutic target for cancer

Abstract

Galectins belong to a family of carbohydrate-binding proteins with an affinity for β-galactosides. Galectin-1 is differentially expressed by various normal and pathologic tissues and displays a wide range of biological activities. In oncology, galectin-1 plays a pivotal role in tumor growth and in the multistep process of invasion, angiogenesis, and metastasis. Evidence indicates that galectin-1 exerts a variety of functions at different steps of tumor progression. Moreover, it has been demonstrated that galectin-1 cellular localization and galectin-1 binding partners depend on tumor localization and stage. Recently, galectin-1 overexpression has been extensively documented in several tumor types and/or in the stroma of cancer cells. Its expression is thought to reflect tumor aggressiveness in several tumor types. Galectin-1 has been identified as a promising drug target using synthetic and natural inhibitors. Preclinical data suggest that galectin-1 inhibition may lead to direct antiproliferative effects in cancer cells as well as antiangiogenic effects in tumors. We provide an up-to-date overview of available data on the role of galectin-1 in different molecular and biochemical pathways involved in human malignancies. One of the major challenges faced in targeting galectin-1 is the translation of current knowledge into the design and development of effective galectin-1 inhibitors in cancer therapy.

Keywords: Angiogenesis; CDC42; Cell transformation; ECM; ERK; Gal-1; Galectin-1; HIF1α; Invasion; JNK; MEK; MMP; Metastasis; NFkB; NRP1; Novel target; PI3K; PKC; ROS; Ras homolog gene family, member A; RhoA; Therapeutic application; VEGFR2; c-Jun NH2-terminal kinases; cell division control protein 42 homolog; extracellular matrix; extracellular-signal-regulated kinase; galectin-1; hypoxia-inducible factor 1-alpha; matrix metalloproteinase; mitogen-activated protein kinase kinase (MAP2K); neuropilin-1; nuclear factor kappa B; phosphoinositide-3-kinase; protein kinase C; reactive oxygen species; tPA; tissue plasminogen activator; vascular endothelial growth factor receptor 2.