Hippo/YAP signaling choreographs the tumor immune microenvironment to promote triple negative breast cancer progression via TAZ/IL-34 axis.
Hippo/YAP signaling choreographs the tumor immune microenvironment to promote triple negative breast cancer progression via TAZ/IL-34 axis.
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DOI：
10.21203/rs.3.rs-524972/v1
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发表时间：
2021-05
期刊：
影响因子：
9.7
通讯作者：
Z. Wang;Fan Wang;Xinxin Ding;Tian-En Li;Hao-Yu Wang;Yu-Hao Gao;Wen-Juan Wang;Yanfen Liu;Xiao-song Chen;K. Shen
中科院分区：
文献类型：
--
作者：
Z. Wang;Fan Wang;Xinxin Ding;Tian-En Li;Hao-Yu Wang;Yu-Hao Gao;Wen-Juan Wang;Yanfen Liu;Xiao-song Chen;K. Shen
越来越多的证据表明，癌细胞与其周围环境，即肿瘤微环境（tumor microenvironment， TME）之间的双向相互作用有助于癌症的进展、转移和对治疗的抵抗。Hippo通路在肿瘤发生过程中控制着多种中枢细胞功能，对其的深入研究主要集中在癌细胞上。然而，在三阴性乳腺癌中，Hippo通路在调节肿瘤-基质相互作用中的作用在很大程度上仍然未知。因此，本研究的重点是揭示Hippo-YAP/TAZ信号对免疫微环境的影响。我们的研究结果表明，Hippo通路的活性与TNBC中更糟糕的疾病结局相关，并可能增加TAM通过TAZ/IL-34轴的浸润，导致免疫抑制微环境并损害抗pd - l1的治疗效果。因此，TAZ/IL-34轴可能作为TNBC患者的新靶点。
Growing evidence suggests that the bidirectional interactions between cancer cells and their surrounding environment, namely the tumor microenvironment (TME), contribute to cancer progression, metastasis, and resistance to treatment. Intense investigation of the Hippo pathway, which controls multiple central cellular functions in tumorigenesis, was focused on cancer cells. However, the role of the Hippo pathway in modulating tumor-stromal interactions in triple-negative breast cancer remains largely unknown. Therefore, this study focused on revealing the effects of Hippo-YAP/TAZ signaling on the immune microenvironment. Our findings reveal that the activity of the Hippo pathway is associated with worse disease outcomes in TNBC and could increase TAM infiltration through the TAZ/IL-34 axis, leading to an immunosuppressive microenvironment and impairing the treatment efficacy of anti-PD-L1. Thus, the TAZ/IL-34 axis may serve as a novel target for TNBC patients.