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Diverse TME elements exchange dynamic bidirectional signals that influence breast cancer growth, invasiveness, and metastasis. The Hedgehog (Hh) pathway, essential in development, is dysregulated in breast cancer initiation, progression, and metastasis. This review summarizes how Hh perturbations affect the breast cancer TME and discusses therapeutic promise and clinical challenges of Hh inhibitors targeting the TME.",{"@graph":69,"@context":122},[70,84,105],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":40,"@type":76,"position":81},"https://docshare.wps.com/document/research-report/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/interactions-between-hedgehog-signaling-pathway-and-the-complex-tumor-microenvironment-in-breast-cancer-current-knowledge-and-therapeutic-promises/332448/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/interactions-between-hedgehog-signaling-pathway-and-the-complex-tumor-microenvironment-in-breast-cancer-current-knowledge-and-therapeutic-promises/332448.png","ImageObject",300,407,{"name":92,"@type":93},"Theodore","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-10-23","2026-09-21",true,{"@type":102,"interactionType":103,"userInteractionCount":24},"InteractionCounter",{"@type":104},"ViewAction",{"@type":106,"mainEntity":107},"FAQPage",[108,114,118],{"name":109,"@type":110,"acceptedAnswer":111},"Why is the tumor microenvironment (TME) important in breast cancer prognosis and therapy?","Question",{"text":112,"@type":113},"The TME contains variable fractions of cancer cells plus host cells, extracellular matrix, and secreted factors. 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Cell Communication and Signaling (2024) 22:432  \n[https://doi.org/10.1186/s12964-024-01812-6](https://doi.org/10.1186/s12964-024-01812-6)  \nCell Communication and Signaling  \nREVIEW Open Access  \nInteractions between hedgehog signaling pathway and the complex tumor microenvironment in breast cancer: current knowledge and therapeutic promises  \nRuijuan Liu1,2†, Yang Yu3†, Qingyang Wang1†, Qianxiang Zhao1, Yan Yao2, Mengxuan Sun1, Jing Zhuang2*, Changgang Sun2,4* and Yuanfu Qi5*  \nAbstract  \nBreast cancer ranks as one of the most common malignancies among women, with its prognosis and therapeutic efficacy heavily influenced by factors associated with the tumor cell biology, particularly the tumor microenvironment (TME) . The diverse elements of the TME are engaged in dynamic bidirectional signaling interactions with various pathways, which together dictate the growth, invasiveness, and metastatic potential of breast cancer. The Hedgehog (Hh) signaling pathway, first identified in Drosophila, has been established as playing a critical role in human development and disease. Notably, the dysregulation of the Hh pathway is recognized as a major driver in the initiation, progression, and metastasis of breast cancer. Consequently, elucidating the mechanisms by which the Hh pathway interacts with the distinct components of the breast cancer TME is essential for comprehensively evaluating the link between Hh pathway activation and breast cancer risk. This understanding is also imperative for devising novel targeted therapeutic strategies and preventive measures against breast cancer. In this review, we delineate the current understanding of the impact of Hh pathway perturbations on the breast cancer TME, including the intricate and complex network of intersecting signaling cascades. Additionally, we focus on the therapeutic promise and clinical challenges of Hh pathway inhibitors that target the TME, providing insights into their potential clinical utility and the obstacles that must be overcome to harness their full therapeutic potential.  \nKeywords Hedgehog signaling pathway, Breast cancer, Tumor microenvironment, Therapeutics  \n†Ruijuan Liu, Yang Yu and Qingyang Wang contributed equally to this work.  \n*Correspondence:  \nJing Zhuang [13963676719@163.com](13963676719@163.com)[ ](13963676719@163.com)Changgang Sun[scgdoctor@126.com](scgdoctor@126.com)[ ](scgdoctor@126.com)Yuanfu Qi [qiyuanfu@163.com](qiyuanfu@163.com)  \n1College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250014, China  \n2Department of Oncology, Weifang Traditional Chinese Hospital, Weifang 261000, China  \n3Faculty of Chinese Medicine, State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Macau 999078, China  \n4College of Traditional Chinese Medicine, Shandong Second Medical University, Weifang 261000, China  \n5Department of Oncology, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, China  \n© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright hold","cbCaicdQSbjVLejp","https://ap.wps.com/l/cbCaicdQSbjVLejp","pdf",2035559,17,"English","# Abstract\n# Introduction","[{\"question\":\"Why is the tumor microenvironment (TME) important in breast cancer prognosis and therapy?\",\"answer\":\"The TME contains variable fractions of cancer cells plus host cells, extracellular matrix, and secreted factors. Bidirectional signaling within the TME helps shape growth, invasiveness, and metastatic potential, affecting treatment outcomes.\"},{\"question\":\"What role does the Hedgehog (Hh) signaling pathway play in breast cancer?\",\"answer\":\"The review describes dysregulated Hh signaling as a major driver of initiation, progression, and metastasis. It is reactivated in a subset of breast cancers and may contribute to tumor immune tolerance and drug resistance.\"},{\"question\":\"What does the review aim to provide about Hh-targeted therapies?\",\"answer\":\"It outlines current knowledge of how Hh pathway perturbations impact the breast cancer TME. It also discusses the therapeutic promise of Hh pathway inhibitors that target the TME, along with clinical challenges to overcome.\"}]","Interactions between hedgehog signaling pathway and the complex tumor microenvironment in breast cancer: current knowledge and therapeutic promises | PDF",1789998237,43]