Beauvericin suppresses the proliferation and pulmonary metastasis of osteosarcoma by selectively inhibiting TGFBR2 pathway.

ABSTRACT: Osteosarcoma (OS) patients, particularly those with distant metastasis, experience rapid progression and derive poor survival benefits from traditional therapies. Currently, effective drugs for treating patients with metastatic OS remain scarce. Here, we found that the cyclic hexadepsipeptide beauvericin (BEA) functioned as a new selective TGFBR2 inhibitor with potent antiproliferative and antimetastatic activities against OS cells. Functionally, BEA inhibited TGF-β signaling-mediated proliferation, invasiveness, mesenchymal phenotype, and extracellular matrix remodeling of OS cells, and suppressed tumor growth and reduced pulmonary metastasis in vivo. Mechanistic investigation revealed that BEA selectively and directly bound to Asn 332 of TGFBR2 and inhibited its kinase acti

SUBMITTER: Ye G 

PROVIDER: S-EPMC10535710 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature