Galectins in Cancer and the Microenvironment: Functional Roles, Therapeutic Developments, and Perspectives

Abstract

Changes in cell growth and metabolism are affected by the surrounding environmental factors to adapt to the cell's most appropriate growth model. However, abnormal cell metabolism is correlated with the occurrence of many diseases and is accompanied by changes in galectin (Gal) performance. Gals were found to be some of the master regulators of cell-cell interactions that reconstruct the microenvironment, and disordered expression of Gals is associated with multiple human metabolic-related diseases including cancer development. Cancer cells can interact with surrounding cells through Gals to create more suitable conditions that promote cancer cell aggressiveness. In this review, we organize the current understanding of Gals in a systematic way to dissect Gals' effect on human disease, including how Gals' dysregulated expression affects the tumor microenvironment's metabolism and elucidating the mechanisms involved in Gal-mediated diseases. This information may shed light on a more precise understanding of how Gals regulate cell biology and facilitate the development of more effective therapeutic strategies for cancer treatment by targeting the Gal family.

Keywords: cancer; galectin; metabolism; tumor microenvironment.

Figure 1

The groups of Gal’s family structures. The distribution of galectin (LGALS) is dependent on the RNA level in the human body. All profiles were collected from the human protein atlas website (https://www.proteinatlas.org/, accessed on 15 September 2020) (see Appendix A).

Figure 2

Pluripotency of the galectin family in hallmarks of cell biology. The schematic diagram illustrates previous Gal functions; Gals are involved in cell proliferation, migration, anti-apoptosis, carbohydrates, proteins, lipid metabolism or nucleic acid synthesis, resistance to drug treatment, immune system or inflammation response, vessel generation, organ fibrogenesis, and resistance to death.

Figure 3

Crosstalk of various signaling molecules that regulate galectin expression. The schematic diagram illustrates the complex regulation involved in Gal expression and interaction components.

Figure 4

Metabolic reprogramming-associated fibrogenesis induction of galectin expression. The schematic diagram illustrates that metabolic reprogramming accompanies organ fibrogenesis and dysregulated Gal expression during stress stimulation.

Figure 5

Galectin family involvement in mitochondrial metabolism reprogramming. Gal expression accompanies both metabolism and microenvironment reprogramming, which can be recognized in several diseases, including tumor progression. ↑ Means increase.

Figure 6

The galectin family contributes to tumor microenvironment reprogramming. Gals can act as a reprogramming messenger to connect tumor cells and other cells in the microenvironment. ↑, ↓ Means increase or decrease.