Wnt Signaling in Cancer Metabolism and Immunity

El-Sahli, Sara; Xie, Ying; Wang, Lisheng; Liu, Sheng

doi:10.3390/cancers11070904

Cited by 94 publications

(87 citation statements)

References 121 publications

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“…Wnt/β-catenin signaling is associated with CSC properties. Activation of Wnt/β-catenin signaling orchestrates the self-renewal of CSCs and induces several stemness factors, such as OCT4, SOX2, and CD44 [114,115]. Members of the secreted frizzled-related protein (SFRP) family are Wnt antagonists and inactivate Wnt ligands, impairing signaling pathways from FZD receptors and low-density lipoprotein receptor-related proteins (LRPs) [114].…”

Section: Wnt/β-catenin Signaling and Cscsmentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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The susceptibility of cancer cells to different types of treatments can be restricted by intrinsic and acquired therapeutic resistance, leading to the failure of cancer regression and remission. To overcome this problem, a combination therapy has been proposed as a fundamental strategy to improve therapeutic responses; however, resistance is still unavoidable. MicroRNA (miRNAs) are associated with cancer therapeutic resistance. The modulation of dysregulated miRNA levels through miRNA-based therapy comprising a replacement or inhibition approach has been proposed to sensitize cancer cells to other anti-cancer therapies. The combination of miRNA-based therapy with other anti-cancer therapies (miRNA-based combinatorial cancer therapy) is attractive, due to the ability of miRNAs to target multiple genes associated with the signaling pathways controlling therapeutic resistance. In this article, we present an overview of recent findings on the role of therapeutic resistance-related miRNAs in different types of cancer. We review the feasibility of utilizing dysregulated miRNAs in cancer cells and extracellular vesicles as potential candidates for miRNA-based combinatorial cancer therapy. We also discuss innate properties of miRNAs that need to be considered for more effective combinatorial cancer therapy.Cells 2020, 9, 29 2 of 32 to confer the ability to acquire CSC properties onto cancer cells, thereby contributing to therapeutic resistance [7]. Moreover, cell-to-cell communication via extracellular vesicles among different types of cells within the cancer microenvironment could affect the efficacy of cancer therapies by delivering miRNAs that regulate various signaling pathways connected to therapeutic resistance [8,9].Combination therapies have been proposed to overcome therapeutic resistance via the combined inhibition of different mechanisms. For example, the combination of cobimetinib and pictilisib was reported to be beneficial for the treatment of colorectal cancer cells. However, resistance is unavoidable even after the combination treatment [10]. Similarly, the simultaneous inhibition of phosphoinositide 3-kinase (PI3K) and a mechanistic target of rapamycin kinase (mTOR) was reported to activate extracellular signal-regulated kinase (ERK), a pro-survival factor, in acute myeloid leukemia [11]. Therefore, it is still necessary to explore new combination strategies to defeat therapeutic resistance. An improved understanding of the cellular basis of cancer therapeutic resistance can further provide promising opportunities to design and develop novel cancer treatment strategies to manage cancers.MicroRNAs (miRNAs) are widely recognized, small, regulatory RNAs modulating numerous intracellular signaling pathways in several diseases, including cancers. Based on the expression levels and intracellular functions of miRNAs, they could act as tumor-suppressive or oncogenic factors in cancer cells [12][13][14]. The abnormal expression of miRNAs is associated with therapeutic resistance in cancer, and the modulation of m...

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Section: Wnt/β-catenin Signaling and Cscsmentioning

confidence: 99%

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Seo

Moeng

Sim³

et al. 2019

Cells

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“…Aberrant Wnt signaling leads to metabolic alterations in cancer cells that are critical for their survival and proliferation (60). Interestingly, Wnt signaling also plays an important role in the metabolic reprogramming of DCs in the TME (60,61). Cellular metabolic pathways play a critical role in modulating the functions of DCs (61)(62)(63).…”

Section: Metabolic Reprogramming Of Dcs By Wntsmentioning

confidence: 99%

“…Cellular metabolic pathways play a critical role in modulating the functions of DCs (61)(62)(63). Emerging evidence show that potential metabolic differences exist among DC subsets and also between tolerogenic and immunogenic DCs (60,62). Immature or tolerogenic DCs show a catabolic metabolism that is manifested by increased oxidative phosphorylation, fatty acid oxidation (FAO), and glutaminolysis (61,63,64).…”

Section: Metabolic Reprogramming Of Dcs By Wntsmentioning

confidence: 99%

“…Emerging studies are beginning to provide insights into the mechanisms by which Wnt signaling cascade directly modulates immunological functions of other immune cells, such as macrophages, myeloid-derived suppressor cells (MDSCs), Tregs, CD4 + T cells, CD8 + T cells, and NK cells (71). There are several excellent studies and reviews that discuss extensively how the Wnt signaling pathway shape the functions of other immune cells (43,44,60,71,72) and will thus be discussed only briefly ( Table 1). Tumor-infiltrating T cells express markedly higher levels of Wnt3a and β-catenin, and display dysfunctional and exhausted effector memory phenotype (28).…”

Section: Effects Of Wnts In Modulating Functions Of Other Immune Cellmentioning

confidence: 99%

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Wnt Signaling Cascade in Dendritic Cells and Regulation of Anti-tumor Immunity

et al. 2020

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Dendritic cells (DCs) control the strength and quality of antigen-specific adaptive immune responses. This is critical for launching a robust immunity against invading pathogens while maintaining a state of tolerance to self-antigens. However, this also represents a fundamental barrier to anti-tumor immune responses and cancer immunotherapy. DCs in the tumor microenvironment (TME) play a key role in this process. The factors in the TME and signaling networks that program DCs to a regulatory state are not fully understood. Recent advances point to novel mechanisms by which the canonical Wnt signaling cascade in DCs regulates immune suppression, and the same pathway in tumors is associated with the evasion of anti-tumor immunity. Here, we review these recent advances in the context of the pleiotropic effects of the Wnts in shaping anti-tumor immune responses by modulating DC functions. In addition, we will discuss how Wnt/β-catenin pathway in DCs can be targeted for successful cancer immunotherapy.Keywords: Wnt, dendritic cells, beta-catenin (β-catenin), tumor microenvironment (TME), immunotherapy, anti-tumor immunity, immunotherapy immunotherapies against a whole range of human cancers.

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“…Wnt signaling pathway seems to play a significant role in immunological reactions (El-Sahli, Xie, Wang, & Liu, 2019), so that it has been shown that stimulation of the Wnt signaling pathway is associated with lower immune cell infiltration in tumor site (Luke, Bao, Sweis, Spranger, & Gajewski, 2019), requiring to expand our understanding towards the Wnt pathway. On the basis of the modulatory impact of Wnt pathway on immunological reactions, targeting this pathway can be beneficial in the treatment of inflammatory disorders such as rheumatoid arthritis (RA).…”

Section: Immunomodulatory Activitymentioning

confidence: 99%

Resveratrol targeting the Wnt signaling pathway: A focus on therapeutic activities

Ashrafizadeh

Ahmadi

Farkhondeh

et al. 2019

Journal Cellular Physiology

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Wingless-type MMTV integration site (Wnt) signaling pathway is considered as an important pathway regulating a variety of biological processes such as tissue formation and homeostasis, cell proliferation, cell migration, cell differentiation, and embryogenesis. Impairment in the Wnt signaling pathway is associated with pathological conditions, particularly cancer. So, modulation of this pathway can be considered as a promising strategy and several drugs have been developed in line with this strategy. Resveratrol (Res) is a naturally occurring nutraceutical compound exclusively found in different fruits and nuts such as grape, peanut, and pistachio. This compound has favorable biological and therapeutic activities such as antioxidant, anti-inflammatory, antitumor, hepatoprotective, cardioprotective, and antidiabetic. At the present review, we demonstrate how Res modulates Wnt signaling pathway to exert its pharmacological effects.

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Wnt Signaling in Cancer Metabolism and Immunity

Cited by 94 publications

References 121 publications

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

MicroRNA-Based Combinatorial Cancer Therapy: Effects of MicroRNAs on the Efficacy of Anti-Cancer Therapies

Wnt Signaling Cascade in Dendritic Cells and Regulation of Anti-tumor Immunity

Resveratrol targeting the Wnt signaling pathway: A focus on therapeutic activities

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