Induction of integrin β3 by sustained ERK activity promotes the invasiveness of TGFβ-induced mesenchymal tumor cells

Hong, Soon-Ki; Park, Jeong-Rak; Kwon, Ok‐Seon; Kim, Keun-Tae; Bae, Gab-Yong; Cha, Hyuk‐Jin

doi:10.1016/j.canlet.2016.04.012

Cited by 24 publications

(22 citation statements)

References 40 publications

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“…EMT widely exists in renal interstitial fibrosis ( 20 ) and liver fibrosis ( 21 ). EMT has a vital role in the recurrence of liver cancer ( 22 ), in addition to the occurrence and metastasis of lung cancer ( 23 ). TGF may be divided into three subtypes in mammals: TGF-β1, TGF-β2 and TGF-β3.…”

Section: Discussionmentioning

confidence: 99%

Effects of bradykinin on TGF‑β1‑induced epithelial‑mesenchymal transition in ARPE‑19 cells

et al. 2018

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The aim of the present study was to investigate the effects of bradykinin (BK) on an epithelial-mesenchymal transition (EMT) model in retinal pigment epithelium (RPE) cells through exposure to transforming growth factor-β1 (TGF-β1). The aim was to improve the effect of BK on proliferative vitreoretinopathy (PVR) progression, and to find a novel method of clinical prevention and treatment for PVR. The morphology of ARPE-19 cells was observed using an inverted phase-contrast microscope. A Cell Counting Kit-8 was used to assess the effects of TGF-β1 on the proliferation of ARPE-19 cells. Western blotting and immunofluorescence were used to detect the expression levels of the epithelial marker E-cadherin, mesenchymal markers α-smooth muscle actin (SMA) and vimentin, and phosphorylated (p) mothers against decapentaplegic homolog (Smad)3 and Smad7 of the TGF/Smad signaling pathway. Wound healing tests and Transwell assays were performed to detect cell migration ability. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis was performed to detect the expression levels of pSmad3 and Smad7 in the TGF/Smad signaling pathway. The results revealed that the addition of 10 ng/ml TGF-β1 resulted in the expression of factors associated with EMT in ARPE-19 cells. BK decreased the expression levels of the mesenchymal markers α-SMA and vimentin, and increased the expression of the epithelial marker E-cadherin. BK decreased cell migration in TGF-β1-induced EMT. These effects were reversed by HOE-140, a specific BK 2 receptor antagonist. BK significantly downregulated the expression of pSmad3 and upregulated the expression of Smad7 in TGF-β1-treated ARPE-19 cells, and the protective alterations produced by BK were inhibited by HOE-140. In conclusion, 10 ng/ml TGF-β1 resulted in EMT in ARPE-19 cells and BK served a negative role in TGF-β1-induced EMT. BK had effects in TGF-β1-induced EMT by upregulating the expression of Smad7 and downregulating the expression of pSmad3 in TGF-β/Smad signaling pathway, indicating that BK may be a novel and effective therapy for PVR.

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Section: Discussionmentioning

confidence: 99%

Effects of bradykinin on TGF‑β1‑induced epithelial‑mesenchymal transition in ARPE‑19 cells

et al. 2018

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“…In the present study, expression levels of integrins αV, α6, and β1 were increased in normal endometrial HES cells following TGF-β1 treatment, but integrin β3 expression was not affected by the same conditions. In A549 lung cancer cells, sustained ERK activity induced by TGF-β1 is involved in the induction of integrin β3 ( 44 ). In the current study, phosphorylation of Smad2 was found to be a major step in the signaling pathway involved in TGF-β1-stimulated integrin expression and endometrial-mesothelial adhesion.…”

Section: Discussionmentioning

confidence: 99%

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

et al. 2017

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Endometriosis is the abnormal growth of endometrial cells outside the uterus, causing pelvic pain and infertility. Furthermore, adhesion of endometrial tissue fragments to pelvic mesothelium is required for the initial step of endometriosis formation outside uterus. TGF-β1 and adhesion molecules importantly function for adhesion of endometrial tissue fragments to mesothelium outside uterus. However, the function of TGF-β1 on the regulation of adhesion molecule expression for adhesion of endometrial tissue fragments to mesothelium has not been fully elucidated. Interestingly, transforming growth factor β1 (TGF-β1) expression was higher in endome-triotic epithelial cells than in normal endometrial cells. The adhesion efficiency of endometriotic epithelial cells to meso-thelial cells was also higher than that of normal endometrial cells. Moreover, TGF-β1 directly induced the adhesion of endometrial cells to mesothelial cells through the regulation of integrin of αV, α6, β1, and β4 via the activation of the TGF-β1/TGF-βRI/Smad2 signaling pathway. Conversely, the adhesion of TGF-β1-stimulated endometrial cells to mesothelial cells was clearly reduced following treatment with neutralizing antibodies against specific TGF-β1-mediated integrins αV, β1, and β4 on the endometrial cell membrane. Taken together, these results suggest that TGF-β1 may act to promote the initiation of endometriosis by enhancing integrin-mediated cell-cell adhesion.

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“…Major developmental signalling pathways, including the TGF-β, Wnt, and growth factor receptor signalling cascades, have been demonstrated to be involved in some aspects of the EMT programme (5,6). Similarly, the MAPK signalling pathway has been confirmed to have an impact on EMT in a variety of tumours, such as CRC, lung cancer and breast cancer (7)(8)(9).…”

Section: Introductionmentioning

confidence: 99%

Paxillin knockdown suppresses metastasis and epithelial‑mesenchymal transition in colorectal cancer via the ERK signalling pathway

Wen

Zhang

et al. 2020

Oncol Rep

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Paxillin (PXN) is a cytoplasmic protein that plays an important role in regulating focal adhesion, cytoskeletal rearrangements and cell motility. The present study aimed to investigate the role of PXN in the metastasis of human colorectal cancer (CRC) and its possible mechanisms. Immunohistochemical staining of tissues from 102 surgical CRC patients revealed that high PXN expression was positively correlated with tumour-node-metastasis (TNM) stage, lymph node metastasis, distant metastasis, and recurrence at distant sites after radical surgery. In 24 cases of stage IV CRC, PXN expression in liver metastasis was higher than that in the matched primary tumour. The knockdown of PXN inhibited the proliferation, migration and invasion potential of SW480 cells in vitro and in vivo. Transmission electron microscopy revealed the effect of PXN on ultrastructural characteristics, observed mainly in microvilli and desmosomes. The downregulation of PXN decreased the activation of extracellular regulated protein kinase (ERK) and suppressed the epithelial-mesenchymal transition (EMT) process. Following the downregulation of PXN, the addition of an ERK activator or inhibitor restored or further suppressed EMT, respectively, accompanied by corresponding changes in cell migration and invasion. Collectively, the present results confirmed the important role of PXN in CRC metastasis and revealed that PXN regulated EMT progression via the ERK signalling pathway. PXN may represent a future therapeutic strategy to prevent the EMT-associated progression and invasion of CRC.

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Induction of integrin β3 by sustained ERK activity promotes the invasiveness of TGFβ-induced mesenchymal tumor cells

Cited by 24 publications

References 40 publications

Effects of bradykinin on TGF‑β1‑induced epithelial‑mesenchymal transition in ARPE‑19 cells

Effects of bradykinin on TGF‑β1‑induced epithelial‑mesenchymal transition in ARPE‑19 cells

Transforming growth factor β1 enhances adhesion of endometrial cells to mesothelium by regulating integrin expression

Paxillin knockdown suppresses metastasis and epithelial‑mesenchymal transition in colorectal cancer via the ERK signalling pathway

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