Small GTPase Arl6 controls RH30 rhabdomyosarcoma cell growth through ciliogenesis and Hedgehog signaling

Abstract

Background: Rhabdomyosarcoma (RMS) originates from skeletal muscle precursors that fail to differentiate. Hedgehog (Hh) signaling and primary cilia contribute to the pathobiology of RMS. Results: Here we showed ADP ribosylation factor like GTPase 6 (ARL6) localizes at the base of primary cilium, controls ciliogenesis and Hh signaling. The transcription of Arl6 is dynamic during the differentiation of myoblasts, companying with the growth and elimination of primary cilia. Arl6 expression is significantly up regulated in cilia-dependent RMS cells and tissues. Knockdown of Arl6 inhibits proliferation and promotes apoptosis of RMS RH30 cells through defected ciliogenesis and reduced Hh activity. Conclusions: Taken together, the functions of Arl6 in ciliogenesis and Hh signaling suggest it as a potential RMS drug target.