A Multifaceted Role for Myd88-Dependent Signaling in Progression of Murine Mammary Carcinoma.
A Multifaceted Role for Myd88-Dependent Signaling in Progression of Murine Mammary Carcinoma.
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DOI：
10.4137/bcbcr.s40075
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Kurt RA
中科院分区：
文献类型：
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作者：
Higgins MJ;Serrano A;Boateng KY;Parsons VA;Phuong T;Seifert A;Ricca JM;Tucker KC;Eidelman AS;Carey MA;Kurt RA
本实验室已有研究表明，在小鼠乳腺癌中可能存在髓系分化初级反应基因88(MyD88)依赖的结构性信号转导通路。在此，我们通过显示，在没有添加Toll样受体激动剂的情况下，4T1肿瘤细胞中形成了肌多体复合体，并且MyD88影响了细胞质外信号调节激酶(ERK)1/ERK2的水平，核因子-kappaB(NF-κB)和信号转导和转录激活因子5(STAT5)的核水平，肿瘤衍生的趋化因子(C-C基序)配体2(CCL2)的表达，以及体外和体内的肿瘤生长。此外，RNA测序显示，MyD88依赖的信号除了抑制能够抑制乳腺癌进展的基因的表达外，还增强了可能导致乳腺癌进展的基因和以前与乳腺癌患者预后不良相关的基因的表达。然而，肿瘤细胞中依赖于MyD88的信号也抑制了可能促进肿瘤进展的基因的表达。总的来说，这些数据揭示了MyD88依赖的信号在小鼠乳腺癌中的多方面作用。
Previous data obtained in our laboratory suggested that there may be constitutive signaling through the myeloid differentiation primary response gene 88 (Myd88)-dependent signaling cascade in murine mammary carcinoma. Here, we extended these findings by showing that, in the absence of an added Toll-like receptor (TLR) agonist, the myddosome complex was preformed in 4T1 tumor cells, and that Myd88 influenced cytoplasmic extracellular signal–regulated kinase (Erk)1/Erk2 levels, nuclear levels of nuclear factor-kappaB (NFκB) and signal transducer and activator of transcription 5 (STAT5), tumor-derived chemokine (C–C motif) ligand 2 (CCL2) expression, and in vitro and in vivo tumor growth. In addition, RNA-sequencing revealed that Myd88-dependent signaling enhanced the expression of genes that could contribute to breast cancer progression and genes previously associated with poor outcome for patients with breast cancer, in addition to suppressing the expression of genes capable of inhibiting breast cancer progression. Yet, Myd88-dependent signaling in tumor cells also suppressed expression of genes that could contribute to tumor progression. Collectively, these data revealed a multifaceted role for Myd88-dependent signaling in murine mammary carcinoma.