STAT3 contributes to lysosomal-mediated cell death in a novel derivative of riccardin D-treated breast cancer cells in association with TFEB

Biochemical Pharmacology
Lin LiHongxiang Lou

Abstract

RDD648, a novel derivative of a natural molecule riccardin D, exhibited potent anticancer activity by targeting lysosomes in vitro and in vivo. Mechanistic studies revealed that RDD648 facilitated STAT3 to translocate into the nucleus, and this activity was involved in lysosome-mediated cell death as evidenced by our finding that inhibition of STAT3 alleviated lysosomal membrane permeabilization. Further investigation indicated that nuclear STAT3 directly interacted with transcription factor TFEB, leading to the partial loss of function of TFEB, which is essential for lysosome turnover. The present study first uncovers that STAT3 contributes to lysosomal-mediated cell death in RDD648-treated breast cancer cells though interacting with TFEB, and the findings may be significant in the design of treatments for breast cancers where STAT3 is constitutively expressed.

Citations

Aug 21, 2018·Traffic·Fengjuan WangPatricia Boya
Nov 16, 2019·PLoS Biology·Toshihiko KobayashiNoriko Toyama-Sorimachi
Dec 17, 2020·Frontiers in Microbiology·Shanshan RaoHongfeng Zhang
Oct 6, 2020·Trends in Biochemical Sciences·Paul Saftig, Rosa Puertollano
Apr 8, 2020·Free Radical Biology & Medicine·Pandian NagakannanEftekhar Eftekharpour
Jun 3, 2021·International Journal of Molecular Sciences·Yanru GuoMargarita Martin

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