Aberrantly expressed Fra-1 by IL-6/STAT3 transactivation promotes colorectal cancer aggressiveness through epithelial–mesenchymal transition

Liu, Hong; Ren, Guoping; Wang, Tingyang; Chen, Yuexia; Gong, Chaoju; Bai, Yanfeng; Wang, Bo; Qi, Hongyan; Shen, Jing; Zhu, Lijun; Qian, Cheng; Lai, Maode; Shao, Jimin

doi:10.1093/carcin/bgv017

Cited by 112 publications

(106 citation statements)

References 50 publications

(54 reference statements)

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“…This p53 downregulation induces EMT-like cellular phenotypic changes, such as a reduction of E-cadherin and an increase of SLUG [143]. Our laboratory also found that aberrant IL-6/STAT3/Fra-1 signaling axis lead to CRC aggressiveness through EMT induction [144]. Besides, the pro-inflammatory cytokine TNF-␣ has been implicated in inducing the EMT in CRC by AKT/GSK-3␤-mediated stabilization of SNAI1, and this finding reinforces the connection between inflammation and the EMT [145].…”

Section: Microenvironmental Regulation Of Emtsupporting

confidence: 54%

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

Cao

Liu

et al. 2015

Pathology - Research and Practice

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Section: Microenvironmental Regulation Of Emtsupporting

confidence: 54%

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

Cao

Liu

et al. 2015

Pathology - Research and Practice

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307

240

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“…Of these inflammatory cytokines, IL‐6 is reported to play especially important roles in the development of lung and breast cancers (Gao et al ., 2007; Sansone et al ., 2007). With regard to the effect of these cytokines on the EMT, previous reports focused mainly on the regulation of EMT‐related downstream factors, with ZEB1 reported as a target gene of certain inflammatory cytokines (Liu et al ., 2015; Peinado et al ., 2007). A recent report suggested that inflammation induces disseminated, dormant cancer cells to form metastatic tumors through functions of ZEB1 (De Cock et al ., 2016).…”

Section: Discussionmentioning

confidence: 99%

ZEB1‐regulated inflammatory phenotype in breast cancer cells

et al. 2017

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Zinc finger E‐box binding protein 1 (ZEB1) and ZEB2 induce epithelial‐mesenchymal transition (EMT) and enhance cancer progression. However, the global view of transcriptional regulation by ZEB1 and ZEB2 is yet to be elucidated. Here, we identified a ZEB1‐regulated inflammatory phenotype in breast cancer cells using chromatin immunoprecipitation sequencing and RNA sequencing, followed by gene set enrichment analysis (GSEA) of ZEB1‐bound genes. Knockdown of ZEB1 and/or ZEB2 resulted in the downregulation of genes encoding inflammatory cytokines related to poor prognosis in patients with cancer, including IL6 and IL8, therefore suggesting that ZEB1 and ZEB2 have similar functions in terms of the regulation of production of inflammatory cytokines. Antibody array and ELISA experiments confirmed that ZEB1 controlled the production of the IL‐6 and IL‐8 proteins. The secretory proteins regulated by ZEB1 enhanced breast cancer cell proliferation and tumor growth. ZEB1 expression in breast cancer cells also affected the growth of fibroblasts in cell culture, and the accumulation of myeloid‐derived suppressor cells in tumors in vivo. These findings provide insight into the role of ZEB1 in the progression of cancer, mediated by inflammatory cytokines, along with the initiation of EMT.

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“…Diesch et al24 found that Fra-1 is strongly expressed in tumor cells at the invasive front of human CRC, and that its depletion suppresses mesenchymal-like features in CRC cells in vitro. Liu et al23 found that aberrantly expressed Fra-1 by IL-6/STAT3 transactivation promotes CRC aggressiveness through EMT. Based on these findings, we speculated that miR-497 might regulate CRC cell EMT, migration, and invasion in part by targeting Fra-1.…”

Section: Discussionmentioning

confidence: 99%

miR-497 suppresses epithelial–mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1

Zhang¹,

Shen²,

Zhang³

2016

OTT

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ObjectiveMicroRNAs have key roles in tumor metastasis. The acquisition of metastatic capability by cancer cells is associated with epithelial–mesenchymal transition (EMT). Here, we describe the role and molecular mechanism of miR-497 in colorectal cancer (CRC) cell EMT, migration, and invasion.MethodsQuantitative real-time polymerase chain reaction and Western blot assays were performed to detect the expression levels of miR-497 and Fos-related antigen-1 (Fra-1) in the CRC cells. HCT116 and SW480 cells with miR-497 overexpression or Fra-1 low expression were constructed by lipofection. Target prediction and luciferase reporter assays were performed to investigate whether Fra-1 is one of the targets of miR-497. Western blot and Transwell assays were performed to detect the effects of miR-497 and Fra-1 on CRC cell EMT, migration and invasion.ResultsWe searched the miRanda, TargetScan, and PicTar databases and found that Fra-1, a key driver of CRC metastasis, is a potential target of miR-497. Quantitative real-time polymerase chain reaction and Western blot analysis verified downregulation of miR-497 and upregulation of Fra-1 in CRC cells. Western blot and Transwell assays showed that overexpression of miR-497 suppresses CRC cell EMT, migration, and invasion. Luciferase gene reporter assay revealed that Fra-1 is a downstream target of miR-497 as miR-497 bound directly to the 3′ untranslated region of Fra-1 messenger RNA. An inverse correlation was also found between miR-497 and Fra-1 in HCT116 and SW480 cells. Furthermore, knockdown of Fra-1 recuperated the effects of miR-497 overexpression.ConclusionmiR-497 suppresses CRC cell EMT, migration, and invasion partly by targeting Fra-1.

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Aberrantly expressed Fra-1 by IL-6/STAT3 transactivation promotes colorectal cancer aggressiveness through epithelial–mesenchymal transition

Cited by 112 publications

References 50 publications

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

ZEB1‐regulated inflammatory phenotype in breast cancer cells

miR-497 suppresses epithelial–mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1

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Aberrantly expressed Fra-1 by IL-6/STAT3 transactivation promotes colorectal cancer aggressiveness through epithelial–mesenchymal transition

Cited by 112 publications

References 50 publications

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

Epithelial–mesenchymal transition in colorectal cancer metastasis: A system review

ZEB1‐regulated inflammatory phenotype in breast cancer cells

miR-497 suppresses epithelial&ndash;mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1

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miR-497 suppresses epithelial–mesenchymal transition and metastasis in colorectal cancer cells by targeting fos-related antigen-1