Sweetening the hallmarks of cancer: Galectins as multifunctional mediators of tumor progression

Abstract

Hanahan and Weinberg have proposed 10 organizing principles that enable growth and metastatic dissemination of cancer cells. These distinctive and complementary capabilities, defined as the “hallmarks of cancer,” include the ability of tumor cells and their microenvironment to sustain proliferative signaling, evade growth suppressors, resist cell death, promote replicative immortality, induce angiogenesis, support invasion and metastasis, reprogram energy metabolism, induce genomic instability and inflammation, and trigger evasion of immune responses. These common features are hierarchically regulated through different mechanisms, including those involving glycosylation-dependent programs that influence the biological and clinical impact of each hallmark. Galectins, an evolutionarily conserved family of glycan-binding proteins, have broad influence in tumor progression by rewiring intracellular and extracellular circuits either in cancer or stromal cells, including immune cells, endothelial cells, and fibroblasts. In this review, we dissect the role of galectins in shaping cellular circuitries governing each hallmark of tumors, illustrating relevant examples and highlighting novel opportunities for treating human cancer.

Targeting Galectins With Glycomimetics

“…Galectins are involved in a wide range of biological activities, such as homeostasis, apoptosis, and vascular embryogenesis (Chan et al, 2018 ). Their involvement in pathological contexts has been described for inflammation (Brinchmann et al, 2018 ), host-pathogen interaction (Vasta, 2009 ), antibacterial autophagy (Weng et al, 2018 ), and cancer (Liu and Rabinovich, 2005 ; Girotti et al, 2020 ). In fact, many members of the family are associated with the phenomena of carcinogenesis being involved in processes such as apoptosis, adhesion, migration, cell transformation, invasion, metastasis, immune escape, and angiogenesis (Dings et al, 2018 ).…”

Hold on or Cut? Integrin- and MMP-Mediated Cell–Matrix Interactions in the Tumor Microenvironment

“…Their abundance in the TME is tested for diagnostic imaging and therapeutic exploitation [ 41 ]. Tenascins and other pericellular ECM proteins, such as periostin [ 42 ], galectins [ 43 ], small integrin-binding ligand N-linked glycoproteins (SIBLINGs), secreted protein acidic and rich in cysteine (SPARC), thrombospondin, angiopoietin-like proteins, certain proteoglycans, and CCN family members are referred to as matricellular proteins [ 44 ]. Rather than performing scaffolding functions, they modulate the supramolecular architecture of the collagen and fibronectin network [ 42 ] and they regulate cellular behavior within the TME [ 37 ].…”

Perspective on dietary isothiocyanates in the prevention, development and treatment of cancer

“…There are documented studies showing targeting of tumor stem cells with good evidence [38,40,43,53] . Furthermore, considering all the hallmark features of cancer originally elaborated by Hanahan and Weinberg [54] and now reviewed and expanded on by Girotti et al [55] , who describe how galectins can affect tumor progression, it is obvious that ITCs can have a significant impact on all of these, including galectins [56] . Thus it is not surprising that there is a building literature on the cancer chemoprevention and anti-tumor progression by ITCs.…”