1. High CLTC expression is associated with worse clinical outcomes in osteosarcoma patients. 2. Inhibition of CLTC suppresses osteosarcoma growth both in vitro and in vivo.3. SP1 binds to the CLTC promoter to promote the transcriptional activity of CLTC in osteosarcoma. 4. CLTC-mediated oncogenic effects occurred through activation of the TGF-beta and AKT/mTOR signaling pathway in a TFG-dependent manner.