Wnt Signaling in the Tumor Microenvironment
Dysregulated Wnt signaling plays a central role in initiation, progression, and metastasis in many types of human cancers. Cancer development and resistance to conventional cancer therapies are highly associated with the tumor microenvironment (TME), whic
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Wnt Signaling in the Tumor Microenvironment Yongsheng Ruan, Heather Ogana, Eunji Gang, Hye Na Kim, and Yong-Mi Kim
Abstract
Keywords
Dysregulated Wnt signaling plays a central role in initiation, progression, and metastasis in many types of human cancers. Cancer development and resistance to conventional cancer therapies are highly associated with the tumor microenvironment (TME), which is composed of numerous stable non-cancer cells, including immune cells, extracellular matrix (ECM), fibroblasts, endothelial cells (ECs), and stromal cells. Recently, increasing evidence suggests that the relationship between Wnt signaling and the TME promotes the proliferation and maintenance of tumor cells, including leukemia. Here, we review the Wnt pathway, the role of Wnt signaling in different components of the TME, and therapeutic strategies for targeting Wnt signaling.
Wnt · β-Catenin · Cancer · Tumor microenvironment · Cancer stem cell · Immune cell · Immune tolerance · Immune evasion · Extracellular matrix · Fibroblast · Endothelial cell · Stromal cell · Therapy
Y. Ruan Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA
7.1
Introduction
The Wnt signaling pathway is a critical regulator of embryogenesis development, tissue homeostasis, stemness control, wound repair, and malignancy [1]. Recently, it was shown that aberrant Wnt signaling is involved in the pathogenesis of cancer, including immune evasion and immunomodulation [2, 3]. The microenvironment of tumor cells is composed of tumor cells, immune cells, and stromal cells, which contribute to drug resistance and survival of the tumor [4]. Here, we review the relationship between aberrant Wnt signaling and the tumor microenvironment (TME) and summarize the potential therapeutic targeting strategies.
Department of Pediatrics, Nanfang Hospital, Southern Medical University, Guangzhou, China H. Ogana · E. Gang · H. N. Kim · Y.-M. Kim (*) Department of Pediatrics, Division of Hematology, Oncology, Blood and Marrow Transplantation, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, CA, USA e-mail: [email protected]
7.2
Wnt Signaling Pathway
The Wnt signaling pathway has been extensively studied and reviewed [1, 5, 6]. In general, there are three pathways: the canonical Wnt pathway,
© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2021 A. Birbrair (ed.), Tumor Microenvironment, Advances in Experimental Medicine and Biology 1270, https://doi.org/10.1007/978-3-030-47189-7_7
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the non-canonical Wnt-planar cell polarity (PCP) pathway, and the non-canonical Wnt-calcium (Ca2+) pathway.
7.2.1 The Canonical Pathway The canonical pathway relies on cytoplasmic β-catenin stabilization [7]. However, β-catenin is a highly unstable protein. In the absence of Wnt ligands, β-catenin is part of the β-catenin destruction complex co
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