National Centre for Cell Science, Savitribai Phule Pune University, Pune, India.
Department of Cancer Biology and Inflammatory Disorder, Indian Institute of Chemical Biology, Kolkata, India.
Front Immunol. 2019 Dec 16;10:2872. doi: 10.3389/fimmu.2019.02872. eCollection 2019.
Wnt signaling is one of the central mechanisms regulating tissue morphogenesis during embryogenesis and repair. The pivot of this signaling cascade is the Wnt ligand, which binds to receptors belonging to the Frizzled family or the ROR1/ROR2 and RYK family. This interaction governs the downstream signaling cascade (canonical/non-canonical), ultimately extending its effect on the cellular cytoskeleton, transcriptional control of proliferation and differentiation, and organelle dynamics. Anomalous Wnt signaling has been associated with several cancers, the most prominent ones being colorectal, breast, lung, oral, cervical, and hematopoietic malignancies. It extends its effect on tumorigenesis by modulating the tumor microenvironment via fine crosstalk between transformed cells and infiltrating immune cells, such as leukocytes. This review is an attempt to highlight the latest developments in the understanding of Wnt signaling in the context of tumors and their microenvironment. A dynamic process known as immunoediting governs the fate of tumor progression based on the correlation of various signaling pathways in the tumor microenvironment and immune cells. Cancer cells also undergo a series of mutations in the tumor suppressor gene, which favors tumorigenesis. Wnt signaling, and its crosstalk with various immune cells, has both negative as well as positive effects on tumor progression. On one hand, it helps in the maintenance and renewal of the leucocytes. On the other hand, it promotes immune tolerance, limiting the antitumor response. Wnt signaling also plays a role in epithelial-mesenchymal transition (EMT), thereby promoting the maintenance of Cancer Stem Cells (CSCs). Furthermore, we have summarized the ongoing strategies used to target aberrant Wnt signaling as a novel therapeutic intervention to combat various cancers and their limitations.
Wnt 信号转导是胚胎发生和修复过程中调节组织形态发生的核心机制之一。该信号级联的核心是 Wnt 配体，它与属于 Frizzled 家族或 ROR1/ROR2 和 RYK 家族的受体结合。这种相互作用控制下游信号级联（经典/非经典），最终将其作用扩展到细胞细胞骨架、增殖和分化的转录控制以及细胞器动力学。异常的 Wnt 信号与几种癌症有关，最突出的是结直肠癌、乳腺癌、肺癌、口腔癌、宫颈癌和血液恶性肿瘤。它通过转化细胞和浸润免疫细胞（如白细胞）之间的精细串扰调节肿瘤微环境，从而对肿瘤发生产生影响。这篇综述试图强调在肿瘤及其微环境背景下理解 Wnt 信号转导的最新进展。一个被称为免疫编辑的动态过程，根据肿瘤微环境和免疫细胞中各种信号通路的相关性，决定了肿瘤进展的命运。癌细胞还会在肿瘤抑制基因中发生一系列突变，有利于肿瘤发生。Wnt 信号转导及其与各种免疫细胞的串扰对肿瘤进展既有正面影响，也有负面影响。一方面，它有助于白细胞的维持和更新。另一方面，它促进免疫耐受，限制抗肿瘤反应。Wnt 信号转导还在上皮-间充质转化（EMT）中发挥作用，从而促进癌症干细胞（CSC）的维持。此外，我们总结了目前用于靶向异常 Wnt 信号作为一种新的治疗干预来对抗各种癌症及其局限性的策略。
