biostudies-literatureUnknown11(6)Shijie LAlthough the treatment of osteosarcoma has improved, the overall survival rate of this common type of osseous malignancies has not changed for four decades. Thus, new targets for better therapeutic regimens are urgently needed. In this study, we found that high expression of clathrin heavy chain (CLTC) was an independent prognostic factor for tumor-free survival (HzR, 3.049; 95% CI, 1.476-6.301) and overall survival (HzR, 2.469; 95% CI, 1.005-6.067) of patients with osteosarcoma. Down-regulation of CLTC resulted in tumor-suppressive effects in vitro and in vivo. Moreover, we found that CLTC was transcriptionally regulated by a transcription factor-specificity protein 1 (SP1), which binds to the CLTC promoter at the -320 to -314-nt and +167 to +173-nt loci. Mechanistic investigations furtheClinical and translational medicinee377https://www.ebi.ac.uk/biostudies/studies/S-EPMC8214859biostudies-literatureDeregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways.PMC8214859Qingcheng YShijie LKang QHua GZhen PDongdong CfalseDeregulation of CLTC interacts with TFG, facilitating osteosarcoma via the TGF-beta and AKT/mTOR signaling pathways.Although the treatment of osteosarcoma has improved, the overall survival rate of this common type of osseous malignancies has not changed for four decades. Thus, new targets for better therapeutic regimens are urgently needed. In this study, we found that high expression of clathrin heavy chain (CLTC) was an independent prognostic factor for tumor-free survival (HzR, 3.049; 95% CI, 1.476-6.301) and overall survival (HzR, 2.469; 95% CI, 1.005-6.067) of patients with osteosarcoma. Down-regulation of CLTC resulted in tumor-suppressive effects in vitro and in vivo. Moreover, we found that CLTC was transcriptionally regulated by a transcription factor-specificity protein 1 (SP1), which binds to the CLTC promoter at the -320 to -314-nt and +167 to +173-nt loci. Mechanistic investigations furthe2021-01-01T00:00:00Z2021 Jun2026-05-08T09:18:00.866Z2025-06-01T00:12:46.145ZS-EPMC82148593418541210.1002/ctm2.377