Glycosphingolipid GM2 Induces Invasiveness in Irradiation-tolerant Lung Cancer Cells

Abstract

Glycans, including glycosphingolipids, are broadly expressed in plasma membranes and play important roles in cell-cell interactions. Recently, it has been revealed that glycans participate in the regulation of malignant phenotypes of cancer cells, e.g. growth and invasion. However, their roles in irradiation-tolerant cancer cells have not yet been elucidated. In this study, we show that specific glycosphingolipids are highly expressed in invasive, irradiation-tolerant lung cancer cells. Particularly, the glycosphingolipid GM2 contributes to the development of an invasive phenotype in these lung cancer cells. Our results suggest that glycosphingolipids, including GM2, are implicated in the regulation of invasiveness in irradiation-tolerant lung cancer cells and may therefore serve as potential therapeutic targets for lung cancers following radiotherapy.

A circular network of coregulated sphingolipids dictates lung cancer growth and progression

“…At the cellular level, we showed that B3GNT5 and GAL3ST1 differentially regulated cancer cell proliferation, migration, invasion, sphere formation as well as in vivo tumor growth. Consistent with this finding, the intracellular level of lacto/neolacto-series glycosphingolipid and sulfatide has been recently implicated in controlling cancer cell properties [40,48]. Interestingly, sphingolipidomics analysis of B3GNT5/GAL3ST1 genetically perturbed lung cancer cell lines confirmed their regulatory role in sphingolipid metabolism, indicating that their expression differentially regulated the synthesis of lacto/neolacto-series glycosphingolipid and sulfatide in order to determine sphingolipid metabolic reprogramming in lung cancer cells.…”

“…After culturing for 24 h, 10 ml CCK-8 reagent was added to each well. Similarly, 100 ml complete medium containing 10 ml CCK-8 solution was added to respective wells at different time points (12,24,36,48 and 60 h). The plates were incubated in dark at 37°C for 2 h, and absorbance at 450 nm wavelength was measured.…”

ADAR1-mediated RNA editing links ganglioside catabolism to glioblastoma stem cell maintenance

“…GM2 gangliosides are glycans. Several functions of glycans have been implicated in cancers (72,73), and GM2 promotes tumor cell invasion and migration (74)(75)(76). GM2 accumulates in lysosomes as a functional consequence of specific mutations in GM2A or its partners in GM2 degradation, HEXA and HEXB (77,78).…”

Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance

“…It has been long known that GM2, which is rather weakly expressed in normal tissue, is highly abundant in several human malignant tumors, including melanomas, gliomas, and neuroblastomas [ 91 ]. Recent studies confirm that GM2 induces invasiveness in irradiation‐tolerant human lung adenocarcinoma cells [ 92 ] and promotes invasion and hence malignancy of human pancreatic ductal adenocarcinoma cells [ 93 ]. In contrast to ganglioside GM2, its direct descendent GM1 was shown to exert anticancerous effects.…”