Galectin-3 and cancer stemness

Glycobiology. 2018 Apr 1;28(4):172-181. doi: 10.1093/glycob/cwy001.

Abstract

Over the last few decades galectin-3, a carbohydrate binding protein, with affinity for N-acetyllactosamine residues, has been unique due to the regulatory roles it performs in processes associated with tumor progression and metastasis such as cell proliferation, homotypic/heterotypic aggregation, dynamic cellular transformation, migration and invasion, survival and apoptosis. Structure-function association of galectin-3 reveals that it consists of a short amino terminal motif, which regulates its nuclear-cytoplasmic shuttling; a collagen α-like domain, susceptible to cleavage by matrix metalloproteases and prostate specific antigen; accountable for its oligomerization and lattice formation, and a carbohydrate-recognition/binding domain containing the anti-death motif of the Bcl2 protein family. This structural complexity permits galectin-3 to associate with numerous molecules utilizing protein-protein and/or protein-carbohydrate interactions in the extra-cellular as well as intracellular milieu and regulate diverse signaling pathways, a number of which appear directed towards epithelial-mesenchymal transition and cancer stemness. Self-renewal, differentiation, long-term culturing and drug-resistance potential characterize cancer stem cells (CSCs), a small cell subpopulation within the tumor that is thought to be accountable for heterogeneity, recurrence and metastasis of tumors. Despite the fact that association of galectin-3 to the tumor stemness phenomenon is still in its infancy, there is sufficient direct evidence of its regulatory roles in CSC-associated phenotypes and signaling pathways. In this review, we have highlighted the available data on galectin-3 regulated functions pertinent to cancer stemness and explored the opportunities of its exploitation as a CSC marker and a therapeutic target.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / metabolism*
  • Galectin 3 / antagonists & inhibitors
  • Galectin 3 / metabolism*
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Galectin 3
  • galectin-3, human