Published on Tue Jul 13 2021

Plexin-A2 Promotes The Proliferation And The Development Of Tumors From Glioblastoma Derived Cells

Neufeld, G., Toledano, S., Sabag, A. D., Liburkin-Dan, T., Kessler, O.

Inhibition of plexin-A2 expression in U87MG glioblastoma cells resulted in strong inhibition of cell proliferation and tumor forming ability. Knock-out of the plexInA2 gene using CRISPR/Cas9 also inhibited cell proliferation which was rescued following re-expression.

2
0
0
Abstract

The semaphorin guidance factors receptor Plexin-A2 transduces sema6A and sema6B signals and when associated with neuropilins can also transduce sema3C signals. Inhibition of plexin-A2 expression in U87MG glioblastoma cells resulted in strong inhibition of cell proliferation and tumor forming ability. Knock-out of the plexin-A2 gene using CRISPR/Cas9 also inhibited cell proliferation which was rescued following re-expression of the plexin-A2 cDNA or expression of a truncated plexin-A2 lacking the extracellular domain. Inhibition of plexin-A2 expression resulted in cell cycle arrest at the G2/M stage, and was accompanied by changes in cytoskeletal organization, cell flattening, and by the expression of senescence associated {beta}-galactosidase. It was also associated with reduced AKT phosphorylation and enhanced phosphorylation of p38MAPK. We find that the pro-proliferative effects of plexin-A2 are mediated by FARP2 and FYN since mutations in the FARP2 binding domain of plexin-A2 or in the FYN phosphorylation sites of plexin-A2 compromised the rescue of the proliferative activity by the plexin-A2 intracellular domain. Our results suggest that plexin-A2 may represent a novel target for the development of anti-tumorigenic therapeutics.