Secretory defects in pediatric osteosarcoma result from downregulation of selective COPII coatomer proteins

Wood, Rachael K.; Flory, Ashley R.; Mann, Melissa J.; Talbot, Lindsay J.; Hendershot, Linda M.

doi:10.1016/j.isci.2022.104100

Cited by 4 publications

(1 citation statement)

References 61 publications

(68 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Lung metastasis is the leading cause of cancer-related death in OS patients. The efficacy of oncogenic kinase-targeted therapies in OS patients is modest and limited due to the high levels of genomic instability in OS cells 1 , 6 , 7 , and these drugs have not been approved for the treatment of OS. Currently, effective drugs for treating OS patients with distant metastasis remain lacking.…”

Section: Introductionmentioning

confidence: 99%

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

Ye,

Jiao,

Deng

et al. 2023

Int. J. Biol. Sci.

View full text Add to dashboard Cite

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 activity, thereby suppressing the aggressive progression of OS cells. Together, our study identifies an innovative and natural selective TGFBR2 inhibitor with effective antineoplastic activity against metastatic OS and demonstrates that targeting TGFBR2 could be a potential therapeutic strategy for metastatic OS.

show abstract

Section: Introductionmentioning

confidence: 99%