英国剑桥大学Jason S. Carroll、Rasmus Siersbæk课题组的最新研究发现，白细胞介素6 （IL6）/ STAT3信号通过干扰雌激素受体α（ER）增强乳腺癌转移。2020年7月16日，《癌细胞》在线发表了这项成果。

研究人员证明IL6 / STAT3信号以不依赖ER的方式诱导ER ⁺乳腺癌细胞转移。STAT3干扰了部分ER增强子以诱导独特的转录程序。尽管STAT3和ER共享这些增强子，但IL6 / STAT3的活性阻碍了以ER为靶点的标准治疗。

相反，使用JAK抑制剂鲁索替尼抑制STAT3活性可减少体内乳腺癌的侵袭。因此，IL6 / STAT3和ER致癌途径在功能上是独立的，这突出了针对IL6 / STAT3靶点在ER ⁺乳腺癌治疗中的潜能。

据了解，IL6及其下游的效应因子STAT3组成了关键的致癌通路，之前研究表明在乳腺癌中该通路与ER功能相关。

附：英文原文

Title: IL6/STAT3 Signaling Hijacks Estrogen Receptor α Enhancers to Drive Breast Cancer Metastasis

Author: Rasmus Siersbk, Valentina Scabia, Sankari Nagarajan, Igor Chernukhin, Evangelia K. Papachristou, Rebecca Broome, Simon J. Johnston, Stacey E.P. Joosten, Andrew R. Green, Sanjeev Kumar, Julia Jones, Soleilmane Omarjee, Ruben Alvarez-Fernandez, Silvia Glont, Sarah J. Aitken, Kamal Kishore, Danya Cheeseman, Emad A. Rakha, Clive DSantos, Wilbert Zwart, Alasdair Russell, Cathrin Brisken, Jason S. Carroll

Issue&Volume: 2020-07-16

Abstract: The cytokine interleukin-6 (IL6) and its downstream effector STAT3 constitute a keyoncogenic pathway, which has been thought to be functionally connected to estrogenreceptor α (ER) in breast cancer. We demonstrate that IL6/STAT3 signaling drives metastasisin ER+ breast cancer independent of ER. STAT3 hijacks a subset of ER enhancers to drivea distinct transcriptional program. Although these enhancers are shared by both STAT3and ER, IL6/STAT3 activity is refractory to standard ER-targeted therapies. Instead,inhibition of STAT3 activity using the JAK inhibitor ruxolitinib decreases breastcancer invasion in vivo. Therefore, IL6/STAT3 and ER oncogenic pathways are functionally decoupled, highlightingthe potential of IL6/STAT3-targeted therapies in ER+ breast cancer.

DOI: 10.1016/j.ccell.2020.06.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(20)30311-1