ILEI is an important intermediate participating in the formation of TGF‐β1–induced renal tubular EMT

Zhao, Xing; Luo, Gang; Fan, Yan; Ma, Xiaoxue; Zhou, Jieqing; Jiang, Hong

doi:10.1002/cbf.3316

Cited by 12 publications

(9 citation statements)

References 38 publications

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“…Although ILEI has been thoroughly described as a tumor autonomous regulator of EMT and invasion, the role of ILEI in paracrine signaling is still unclear ( 25 , 28 , 29 , 33 , 43 – 45 ). Our characterization of the novel vemurafenib–USF-1–ILEI regulatory axis has implications for paracrine ILEI signaling.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1)

Noguchi

Dincman

Dalton

et al. 2018

Journal of Biological Chemistry

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Interleukin-like EMT inducer (ILEI, FAM3C) is a secreted factor that contributes to the epithelial-to-mesenchymal transition (EMT), a cell-biological process that confers metastatic properties to a tumor cell. However, very little is known about how ILEI is regulated. Here we demonstrate that ILEI is an in vivo regulator of melanoma invasiveness and is transcriptionally up-regulated by the upstream stimulatory factor-1 (USF-1), an E-box–binding, basic-helix-loop-helix family transcription factor. shRNA-mediated knockdown of ILEI in melanoma cell lines attenuated lung colonization but not primary tumor formation. We also identified the mechanism underlying ILEI transcriptional regulation, which was through a direct interaction of USF-1 with the ILEI promoter. Of note, stimulation of endogenous USF-1 by UV-mediated activation increased ILEI expression, whereas shRNA-mediated USF-1 knockdown decreased ILEI gene transcription. Finally, we report that knocking down USF-1 decreases tumor cell migration. In summary, our work reveals that ILEI contributes to melanoma cell invasiveness in vivo without affecting primary tumor growth and is transcriptionally up-regulated by USF-1.

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Section: Resultsmentioning

confidence: 99%

Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1)

Noguchi

Dincman

Dalton

et al. 2018

Journal of Biological Chemistry

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“…In the renal tubular cell line HK2, FAM3C can independently induce EMT via the Akt-signaling pathway. Knockdown of FAM3C enhances the expression of E-cadherin and suppresses the phosphorylation of Akt 8. FAM3C overexpression has been reported to induce Akt phosphorylation in HepG2 cells 9.…”

Section: Introductionmentioning

confidence: 99%

Elevated FAM3C promotes cell epithelial–mesenchymal transition and cell migration in gastric cancer

Shi¹,

Duan²,

Nie³

et al. 2018

OTT

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BackgroundTumor metastasis is an important factor in treatment failure for advanced gastric cancer. Family with sequence similarity 3 member C (FAM3C) is known to play a critical role in inducing epithelial–mesenchymal transition in several cancer types, while its role in gastric cancer is unidentified. The aim of this study was to investigate the role of FAM3C in gastric cancer and provide new information on the receptor tyrosine-kinase pathway and cytokine-based therapies.MethodsFAM3C expression was tested in human gastric cancer tissue and adjacent normal mucosa, and the prognostic effect of FAM3C was analyzed in data from the Cancer Genome Atlas (TCGA). The role of FAM3C in gastric cancer proliferation and metastasis was investigated in vitro and in vivo. Western blot analysis and immunofluorescence were used to detect the underlying mechanisms.ResultsFAM3C expression was increased in gastric cancer tissue and showed cytoplasmic distribution. Gastric cancer patients with FAM3C overexpression had significantly worse prognoses based on TCGA data. In the gastric cancer cell lines MKN45 and AGS, knockdown of FAM3C dramatically attenuated cell migration, but had almost no influence on proliferation, while exogenous FAM3C promoted cell migration in a cell line with low FAM3C expression. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of TCGA data showed that FAM3C was mainly associated with genes involved in focal adhesion, extracellular matrix–receptor interactions and the PI3K–Akt signaling pathway. Knockdown of FAM3C in gastric cancer cell lines significantly suppressed epithelial–mesenchymal transition, as demonstrated by increased expression of E-cadherin and decreased expression of Snail and Slug. Furthermore, knockdown of FAM3C strongly suppressed activation of the PI3K–Akt signaling pathway. Finally, we confirmed that FAM3C knockdown significantly decreased metastatic lesions in vivo.ConclusionOur study demonstrated that FAM3C can promote gastric cancer metastasis both in vitro and in vivo. FAM3C should be taken into consideration for gastric cancer treatments involving inhibition of the ligands and downstream pathways of receptor tyrosine kinases.

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“…More and more evidences showed that EMT is a typical feature of renal fibrosis, and EMT of tubular epithelial cells contributes significantly to the occurrence, development, and pathological processes of kidney fibrosis (Sharma, 2014;Sun et al, 2017). Transforming growth factor-β1 (TGF-β1) is a typical pro-fibrotic cytokine involved in the process of EMT (Zhao et al, 2018). Studies had shown that TGF-β1 participates in the EMT process by activating the TGF-β1/Smad signaling pathway (Du et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

et al. 2020

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Renal tubulointerstitial fibrosis is usually the final outcome of various end-stage renal diseases. Recent studies have reported that microRNAs (miRNAs) play an important role in renal fibrosis. However, the biological function of microRNAs in renal fibrosis is complicated and remains unclear. In this study, our results show that miR-140-5p expression is significantly down-regulated in mice with unilateral ureteral obstruction and human proximal tubule epithelial cells (HK2) treated with TGF-β1. The knockdown of miR-140-5p upregulates the expression levels of collagen I, collagen IV, and α-SMA, decreases E-cadherin expression, and increases Smad-2/3 phosphorylation. In contrast, the overexpression of miR-140-5p decreases the expression levels of collagen I, collagen IV, and α-SMA, enhances E-cadherin expression, and inhibits the phosphorylation of Smad-2/3 in HK2 cells treated with TGF-β1. The dual-luciferase reporter assay revealed that TGFBR1 is a direct target gene of miR-140-5p. The enforced expression of miR-140-5p significantly inhibited the expression of TGFBR1 in HK2 cells. Furthermore, the knockdown of TGFBR1 has a similar effect of miR-140-5p overexpression on blocking the TGF-β1/smad signal pathway activation. In contrast, the overexpression of TGFBR1 reverses the effect of miR-140-5p inhibition on the activation of the TGF-β1/smad signal pathway. This study demonstrates that miR-140-5p regulates the TGF-β1/smad signaling pathway by suppressing the expression of TGFBR1. Therefore, miR-140-5p may have a therapeutic potential for preventing fibrotic kidney diseases through inhibiting the TGF-β1/Smad signaling pathway by directly targeting TGFBR1.

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ILEI is an important intermediate participating in the formation of TGF‐β1–induced renal tubular EMT

Cited by 12 publications

References 38 publications

Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1)

Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1)

Elevated FAM3C promotes cell epithelial–mesenchymal transition and cell migration in gastric cancer

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

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ILEI is an important intermediate participating in the formation of TGF‐β1–induced renal tubular EMT

Cited by 12 publications

References 38 publications

Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1)

Interleukin-like EMT inducer (ILEI) promotes melanoma invasiveness and is transcriptionally up-regulated by upstream stimulatory factor-1 (USF-1)

Elevated FAM3C promotes cell epithelial&ndash;mesenchymal transition and cell migration in gastric cancer

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-β1/Smad Signaling Pathway by Directly Targeting TGFBR1

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Elevated FAM3C promotes cell epithelial–mesenchymal transition and cell migration in gastric cancer