STAT3 contributes to lysosomal-mediated cell death in a novel derivative of riccardin D-treated breast cancer cells in association with TFEB
STAT3 contributes to lysosomal-mediated cell death in a novel derivative of riccardin D-treated breast cancer cells in association with TFEB
复制标题
STAT3 与 TFEB 相关，在 riccardin D 处理的乳腺癌细胞的新型衍生物中促进溶酶体介导的细胞死亡
DOI：
10.1016/j.bcp.2018.02.026
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发表时间：
2018-04-01
影响因子：
5.8
通讯作者：
Lou, Hongxiang
中科院分区：
文献类型：
--
作者：
Li, Lin;Sun, Bin;Lou, Hongxiang
RDD 648是一种天然分子里卡多素D的新型衍生物，在体外和体内都表现出了很强的抗肿瘤活性。机制研究表明，RDD 648促进STAT3易位到细胞核中，并且这种活性参与溶酶体介导的细胞死亡，如我们发现抑制STAT3减轻溶酶体膜透化所证明的。进一步的研究表明，核STAT3直接与转录因子TFEB相互作用，导致TFEB的部分功能丧失，这是溶酶体周转所必需的。本研究首次揭示了STAT3通过与TFEB相互作用促进RDD 648处理的乳腺癌细胞中溶酶体介导的细胞死亡，并且该发现可能在设计STAT3组成型表达的乳腺癌治疗方法中具有重要意义。
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.