Galectins and galectin-mediated autophagy regulation: new insights into targeted cancer therapy

Abstract

Galectins are animal lectins with specific affinity for galactosides via the conserved carbohydrate recognition domains. Increasing studies recently have identified critical roles of galectin family members in tumor progression. Abnormal expression of galectins contributes to the proliferation, metastasis, epithelial-mesenchymal transformation (EMT), immunosuppression, radio-resistance and chemoresistance in various cancers, which has attracted cumulative clinical interest in galectin-based cancer treatment. Galectin family members have been reported to participate in autophagy regulation under physiological conditions and in non-tumoral diseases, and implication of galectins in multiple processes of carcinogenesis also involves regulation of autophagy, however, the relationship between galectins, autophagy and cancer remains largely unclear. In this review, we introduce the structure and function of galectins at the molecular level, summarize their engagements in autophagy and cancer progression, and also highlight the regulation of autophagy by galectins in cancer as well as the therapeutic potentials of galectin and autophagy-based strategies. Elaborating on the mechanism of galectin-regulated autophagy in cancers will accelerate the exploitation of galectins-autophagy targeted therapies in treatment for cancer.

Galectin inhibitors and nanoparticles as a novel therapeutic strategy for glioblastoma multiforme

“…Gal-8 also plays a role in autophagy, which is a natural cellular recycling process that aids in cell survival and maintenance [52]. In the context of glioblastoma multiforme, Gal-8 may play a role in promoting glioblastoma cell autophagy, thereby augmenting cell growth [53]. The mechanism through which Gal-8 promotes autophagy may be elucidated in the setting of neurodegenerative disease [54].…”

“…Gal-8 assists in autophagy through detecting endomembrane damage and recruiting cargo receptor nuclear dot protein 52 (NDP52). Recruitment of NDP52 in turn initiates autophagy through the UNC51-like kinase-1 (ULK1) and TANK-binding kinase 1 (TBK1) complexes, resulting in the phosphorylation of downstream protein and receptors mediating autophagy [53,[55][56][57].…”

The Pivotal Role of Galectin-3 in Viral Infection: A Multifaceted Player in Host–Pathogen Interactions

“…Galectin-3 can also influence host cell survival and death mechanisms, such as apoptosis and autophagy [28,37]. Although the anti-apoptotic function of Gal-3 has been widely reported in various pathological processes, its role in virus-infected cells and its potential contribution to viral replication and persistence remain unclear [38].…”

“…On the other hand, Gal-3 has been implicated in the regulation of autophagy, a cellular process that can promote viral clearance through degrading viral components [37]. Notably, in adenovirus infections, Gal-3 has been demonstrated to suppress autophagic activation [39].…”

Time-course analysis of liver and serum galectin-3 in acute liver injury after alpha-galactosylceramide injection

“…Their roles are diverse and include intercellular and cell-matrix adhesion, regulation of cell proliferation, apoptosis, mRNA splicing, signal transduction, and immune regulation [ 3 ]. Galectins’ roles in angiogenesis, cell migration, and tumor immune evasion during carcinogenesis are also closely related to cancer biology, and galectins have recently attracted much attention in the field of cancer research and therapy [ 4 , 5 ]. Galectins, soluble proteins, play important regulatory roles inside and outside the cell.…”