p38γ overexpression promotes osteosarcoma cell progression

Osteosarcoma (OS) is the most common primary bone malignancy in the adolescent population. Recent studies demonstrate that p38 gamma (p38 gamma) phosphorylates retinoblastoma (Rb) to promote cyclin expression, cell-cycle entry and tumorigenesis. Studying the potential function of p38 gamma in human OS, we show that p38 gamma mRNA and protein expression are significantly elevated in OS tissues and OS cells, whereas its expression is relatively low in normal bone tissue and in human osteoblasts/osteoblastic cells. Knockdown of p38 gamma in established (U2OS) and primary human OS cells potently inhibited cell growth, proliferation, migration and invasion, while promoting cell apoptosis. Furthermore, CRISPR/Cas9-induced p38 gamma knockout inhibited human OS cell progression in vitro. Conversely, ectopic overexpression of p38 gamma in primary human OS cells augmented cell growth, proliferation and migration. Signaling studies show that retinoblastoma (Rb) phosphorylation and cyclin E1/cyclin A expression were decreased following p38 gamma shRNA knockdown and knockout, but increased after ectopic p38 gamma overexpression. Collectively, these results show that p38 gamma overexpression promotes human OS cell progression.