Ruxolitinib induces apoptosis and pyroptosis of anaplastic thyroid cancer via the transcriptional inhibition of DRP1-mediated mitochondrial fission

• DOI: 10.1038/s41419-024-06511-1
• Publication Date: 2024-02-09T19:02:17Z
• Authors: Ya-wen Guo; Lei Zhu; Yan-ting Duan; Yi-qun Hu; Le-bao Li; Wei-jiao Fan; Fa-huan Song; Ye-feng Cai; Yun-ye Liu; Guo-wan Zheng; Ming-hua Ge
• Keywords: Anaplastic thyroid cancer; Pyroptosis

Abstract Anaplastic thyroid carcinoma (ATC) has a 100% disease-specific mortality rate. The JAK1/2-STAT3 pathway presents promising target for treating hematologic and solid tumors. However, it is unknown whether the activated in ATC, anti-cancer effects mechanism of action its inhibitor, ruxolitinib (Ruxo, clinical JAK1/2 inhibitor), remain elusive. Our data indicated that signaling significantly upregulated ATC tumor tissues than normal papillary cancer tissues. Apoptosis GSDME-pyroptosis were observed cells following vitro vivo administration Ruxo. Mechanistically, Ruxo suppresses phosphorylation STAT3, resulting repression DRP1 transactivation causing mitochondrial fission deficiency. This deficiency essential activating caspase 9/3-dependent apoptosis GSDME-mediated pyroptosis within cells. In conclusion, our findings indicate directly regulated transactivated by STAT3; this exhibits novel crucial aspect on regulation dynamics. transcriptional inhibition hampered division triggered through mechanisms. These results provide compelling evidence potential therapeutic effectiveness ATC.