4.5 Article

Tumor-Induced STAT3 Signaling in Myeloid Cells Impairs Dendritic Cell Generation by Decreasing PKCβII Abundance

期刊

SCIENCE SIGNALING
卷 7, 期 313, 页码 -

出版社

AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scisignal.2004656

关键词

-

资金

  1. NIH [R01 CA140622, R01 CA121044, R01 AI10015, T32 CA085183]
  2. Multiple Myeloma Research Foundation
  3. Roswell Park Cancer Institute Alliance Foundation

向作者/读者索取更多资源

A major mechanism by which cancers escape control by the immune system is by blocking the differentiation of myeloid cells into dendritic cells (DCs), immunostimulatory cells that activate antitumor T cells. Tumor-dependent activation of signal transducer and activator of transcription 3 (STAT3) signaling in myeloid progenitor cells is thought to cause this block in their differentiation. In addition, a signaling pathway through protein kinase C beta II (PKC beta II) is essential for the differentiation of myeloid cells into DCs. We found in humans and mice that breast cancer cells substantially decreased the abundance of PKCbII in myeloid progenitor cells through a mechanism involving the enhanced activation of STAT3 signaling by soluble, tumor-derived factors (TDFs). STAT3 bound to previously undescribed negative regulatory elements within the promoter of PRKCB, which encodes PKC beta II. We also found a previously undescribed counter-regulatory mechanism through which the activity of PKC beta II inhibited tumor-dependent STAT3 signaling by decreasing the abundance of cell surface receptors, such as cytokine and growth factor receptors, that are activated by TDFs. Together, these data suggest that a previously unrecognized cross-talk mechanism between the STAT3 and PKC beta II signaling pathways provides the molecular basis for the tumor-induced blockade in the differentiation of myeloid cells, and suggest that enhancing PKC beta II activity may be a therapeutic strategy to alleviate cancer-mediated suppression of the immune system.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.5
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据