Tumor cell intrinsic RON signaling suppresses innate immune responses in breast cancer through inhibition of IRAK4 signaling.
Tumor cell intrinsic RON signaling suppresses innate immune responses in breast cancer through inhibition of IRAK4 signaling.
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DOI：
10.1016/j.canlet.2021.01.019
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发表时间：
2021-04-10
期刊：
影响因子：
9.7
通讯作者：
Waltz SE
中科院分区：
文献类型：
--
作者：
Bourn JR;Ruiz-Torres SJ;Hunt BG;Benight NM;Waltz SE
越来越多的证据表明，癌细胞需要改变内在的细胞过程和肿瘤微环境，以实现肿瘤的建立、生长和向转移性疾病的进展。尽管如此，控制肿瘤细胞过程以及肿瘤微环境的肿瘤细胞内在分子机制的知识是有限的。在这项研究中，我们提供的证据表明，罗恩信号在调节乳腺癌的发生，发展和转移，通过调节肿瘤细胞的内在过程和肿瘤微环境的新作用。使用临床相关的乳腺癌模型，我们表明，罗恩信号在乳腺上皮肿瘤细胞促进肿瘤细胞的存活和增殖，以及与减少M1巨噬细胞，自然杀伤（NK）细胞，和CD8+ T细胞募集免疫许可的微环境。此外，我们证明了罗恩信号通过新的机制支持这些表型，包括抑制IRAK 4信号和抑制I型干扰素。我们的研究表明，乳腺癌细胞内罗恩信号传导的激活促进肿瘤细胞内在生长和免疫逃避，这支持乳腺癌进展，并突出了靶向罗恩信号传导作为针对乳腺癌的潜在治疗策略的作用。
Increasing evidence suggests that cancer cells require both alterations in intrinsic cellular processes and the tumor microenvironment for tumor establishment, growth, and progression to metastatic disease. Despite this, knowledge of tumor-cell intrinsic molecular mechanisms controlling both tumor cell processes as well as the tumor microenvironment is limited. In this study, we provide evidence demonstrating the novel role of RON signaling in regulating breast cancer initiation, progression, and metastasis through modulation of tumor cell intrinsic processes and the tumor microenvironment. Using clinically relevant models of breast cancer, we show that RON signaling in the mammary epithelial tumor cells promotes tumor cell survival and proliferation as well as an immunopermissive microenvironment associated with decreased M1 macrophage, natural killer (NK) cell, and CD8+ T cell recruitment. Moreover, we demonstrate that RON signaling supports these phenotypes through novel mechanisms involving suppression of IRAK4 signaling and inhibition of type I Interferons. Our studies indicate that activation of RON signaling within breast cancer cells promotes tumor cell intrinsic growth and immune evasion which support breast cancer progression and highlight the role of targeting RON signaling as a potential therapeutic strategy against breast cancer.
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影响因子：
4.7
作者：
Budhwani M;Mazzieri R;Dolcetti R
通讯作者：
Dolcetti R
DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
影响因子：
--
作者：
Benight NM;Wagh PK;Zinser GM;Peace BE;Stuart WD;Vasiliauskas J;Pathrose P;Starnes SL;Waltz SE
通讯作者：
Waltz SE
影响因子：
28.4
作者：
Adams S;Gatti-Mays ME;Kalinsky K;Korde LA;Sharon E;Amiri-Kordestani L;Bear H;McArthur HL;Frank E;Perlmutter J;Page DB;Vincent B;Hayes JF;Gulley JL;Litton JK;Hortobagyi GN;Chia S;Krop I;White J;Sparano J;Disis ML;Mittendorf EA
通讯作者：
Mittendorf EA
影响因子：
14.9
作者：
Chen J;Bardes EE;Aronow BJ;Jegga AG
通讯作者：
Jegga AG