Interleukin-23 promotes the epithelial-mesenchymal transition of oesophageal carcinoma cells via the Wnt/β-catenin pathway

Chen, Deyu; Li, Wei; Liu, Shenzha; Su, Yuting; Han, Guohu; Xu, Chenchen; Liu, Hongli; Zheng, Tingting; Zhou, Yuepeng; Mao, Chaoming

doi:10.1038/srep08604

Cited by 38 publications

(51 citation statements)

References 37 publications

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“…In addition to these strategies, we suggest that the IL23-producing tumor-mediated conversion from ILC1 into ILC3 is a novel strategy of tumors that favors tumor progression and expansion in the TME. Similar to lung cancer, SqCCs in the esophagus also express IL23, contributing to the epithelialmesenchymal transition via the Wnt/b-catenin pathway (33). Thus, these findings suggest that IL23 produced by SqCCs has diverse effects on tumorigenesis and progression by regulating intrinsic tumor biology and cross-talk with extrinsic immune cells, which suggests that the IL23-ILC3 axis may be a therapeutic target for IL23-producing SqCCs.…”

Section: Discussionmentioning

confidence: 81%

IL23-Producing Human Lung Cancer Cells Promote Tumor Growth via Conversion of Innate Lymphoid Cell 1 (ILC1) into ILC3

Koh

Kim

Lee

et al. 2019

Clinical Cancer Research

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Purpose: The plasticity of innate lymphoid cells (ILCs) has been reported in vitro and in the microenvironment of the intestine. However, whether ILC plasticity contributes to regulation of the tumor microenvironment remains unknown. In this study, we explored plasticity of ILCs in human lung cancer. Experimental Design: We analyzed immune subsets and cytokine expression in lung cancers freshly obtained from 80 patients and explored conversion of ILC1 into ILC3 in coculture with lung cancer cells. Prognostic effects of converted ILC3 and related pathway were evaluated by retrospective cohort composed of 875 patients with lung cancer. Results: Low percentages of ILC1, and high percentages of ILC3 were found in pulmonary squamous cell carcinomas (SqCC) but not adenocarcinomas (ADC). In non-small-cell lung cancers, the percentage of ILC3 was associated with IL23 expression in tumor cells but not immune cells. In cocultures, tumor cells of SqCCs converted ILC1 into ILC3 by producing IL23, thus promoting IL17-mediated tumor cell proliferation. Consistently, among IL17 þ immune cells, the percentages of ILCs were higher in SqCCs than ADCs. Furthermore, the numbers of CD3 À RORgt þ ILC3, IL17 expression level, and IL23-or IL17RA-expressing tumor cells were associated with short survival of patients with SqCC but not ADC. Conclusions: Conversion from ILC1 into ILC3 by IL23producing SqCCs promotes IL17-mediated tumor progression, resulting in a poor prognosis.

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Section: Discussionmentioning

confidence: 81%

IL23-Producing Human Lung Cancer Cells Promote Tumor Growth via Conversion of Innate Lymphoid Cell 1 (ILC1) into ILC3

Koh

Kim

Lee

et al. 2019

Clinical Cancer Research

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“…Tumor infiltration by the proinflammatory Th17 T cells is associated with increased Th17‐associated cytokines IL‐23, IL‐17, IL‐1β, and IL‐6. In esophageal cancer, IL‐23 expression in the primary tumor relates to the presence of nodal and distance metastases (Chen et al ., ). In vitro , treatment of esophageal cancer cell lines with recombinant IL‐23 induces EMT‐like changes characterized by loss of E‐cadherin and de novo vimentin expression (Chen et al ., ).…”

Section: Emt and Soluble Factors Of Inflammationmentioning

confidence: 97%

“…In esophageal cancer, IL‐23 expression in the primary tumor relates to the presence of nodal and distance metastases (Chen et al ., ). In vitro , treatment of esophageal cancer cell lines with recombinant IL‐23 induces EMT‐like changes characterized by loss of E‐cadherin and de novo vimentin expression (Chen et al ., ). The signaling pathways in these cells comprise activation of the Wnt/β‐catenin pathway, subsequent GSK‐3β stabilization, which finally triggers Slug and Snail1 expression (Fig.…”

Section: Emt and Soluble Factors Of Inflammationmentioning

confidence: 97%

EMT and inflammation: inseparable actors of cancer progression

et al. 2017

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Tumors can be depicted as wounds that never heal, and are infiltrated by a large array of inflammatory and immune cells. Tumor‐associated chronic inflammation is a hallmark of cancer that fosters progression to a metastatic stage, as has been extensively reviewed lately. Indeed, inflammatory cells persisting in the tumor establish a cross‐talk with tumor cells that may result in a phenotype switch into tumor‐supporting cells. This has been particularly well described for macrophages and is referred to as tumor‐associated ‘M2’ polarization. Epithelial‐to‐mesenchymal transition (EMT), the embryonic program that loosens cell–cell adherence complexes and endows cells with enhanced migratory and invasive properties, can be co‐opted by cancer cells during metastatic progression. Cancer cells that have undergone EMT are more aggressive, displaying increased invasiveness, stem‐like features, and resistance to apoptosis. EMT programs can also stimulate the production of proinflammatory factors by cancer cells. Conversely, inflammation is a potent inducer of EMT in tumors. Therefore, the two phenomena may sustain each other, in an alliance for metastasis. This is the focus of this review, where the interconnections between EMT programs and cellular and molecular actors of inflammation are described. We also recapitulate data linking the EMT/inflammation axis to metastasis.

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“…1g). We have previously suggested that aberrant IL-23 expression enhances the activity of EMT in ESCCs [14]. Therefore, IL-23 mediates the trans-differentiation not only by affecting the accumulation of stem-like makers but also by directionally inducing the expression of stemness-related genes in IL-23R + ESCCs.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-23 receptor signaling mediates cancer dormancy and radioresistance in human esophageal squamous carcinoma cells via the Wnt/Notch pathway

Zhou

Zhu

et al. 2018

J Mol Med

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In the tumor microenvironment, inflammatory cells and molecules influence almost every process; among them, interleukin-23 (IL-23) is a pro-inflammatory molecule that exhibits pro- or anti-tumor properties, but both activities remain poorly understood. In this study, we investigated the effect of extracellular IL-23 in IL-23 receptor-positive (IL-23R+) esophageal squamous cell carcinoma (ESCC) and explored the mechanisms underlying this effect. We analyzed ESCC tumor tissues by immunohistochemical and immunofluorescence staining and found that IL-23, which was highly expressed, co-localized with Oct-4A in IL-23R+ ESCC cells. In addition, IL-23 treatment significantly increased the accumulation of CD133+ cells and activated the Wnt and Notch signaling pathways in CD133−IL-23R+ ESCC cell lines. Consistently, CD133−IL-23R+ cells pretreated with IL-23 showed stronger anti-apoptosis activity when exposed to radiation and higher survival than untreated groups. Moreover, the inhibition of Wnt/Notch signaling by a small-molecule inhibitor or siRNA abolished the effect of IL-23-induced dormancy and consequent radioresistance. Taken together, these results suggested that IL-23 facilitates radioresistance in ESCC by activating Wnt/Notch-mediated G0/1 phase arrest, and attenuating these detrimental changes by blocking the formation of dormancy may prove to be an effective pretreatment for radiotherapy.Key messages IL-23/IL-23R is correlated with the acquisition of stem-like potential in ESCC.CD133−IL-23R+ ESCCs acquired dormancy via IL-23.Radioresistance depends on IL-23-mediated Wnt/Notch pathway activation in vitro and vivo. Electronic supplementary materialThe online version of this article (10.1007/s00109-018-1724-8) contains supplementary material, which is available to authorized users.

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Interleukin-23 promotes the epithelial-mesenchymal transition of oesophageal carcinoma cells via the Wnt/β-catenin pathway

Cited by 38 publications

References 37 publications

IL23-Producing Human Lung Cancer Cells Promote Tumor Growth via Conversion of Innate Lymphoid Cell 1 (ILC1) into ILC3

IL23-Producing Human Lung Cancer Cells Promote Tumor Growth via Conversion of Innate Lymphoid Cell 1 (ILC1) into ILC3

EMT and inflammation: inseparable actors of cancer progression

Interleukin-23 receptor signaling mediates cancer dormancy and radioresistance in human esophageal squamous carcinoma cells via the Wnt/Notch pathway

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