Glucocorticoids ameliorate TGF-β1-mediated epithelial-to-mesenchymal transition of airway epithelium through MAPK and Snail/Slug signaling pathways

Yang, Hyun Woo; Lee, Seoung Ae; Shin, Jae Min; Park, Il Ho; Lee, Heung Man

doi:10.1038/s41598-017-02358-z

Cited by 48 publications

(40 citation statements)

References 44 publications

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“…Down regulation of E-cadherin and up regulation of N-cadherin are the major molecular events regarding the reduction in cell-cell adhesion and facilitation of cell movement [ 49 , 50 ]. In addition, vimentin is an important protein regulator of EMT and the down-regulation of vimentin has been shown to decrease cell migration and transcription factors of EMT, such as snail and slug [ 51 – 53 ]. In this study, we found that phoyunnanin E could reverse the E-cadherin to N-cadherin switch and reduce vimentin and the related EMT transcription factors, snail and slug (Fig.…”

Section: Discussionmentioning

confidence: 99%

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3

Petpiroon

Sritularak

Chanvorachote

2017

BMC Complement Altern Med

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BackgroundThe conversion of the epithelial phenotype of cancer cells into cells with a mesenchymal phenotype-so-called epithelial–mesenchymal transition (EMT)-has been shown to enhance the capacity of the cells to disseminate throughout the body. EMT is therefore becoming a potential target for anti-cancer drug discovery. Here, we showed that phoyunnanin E, a compound isolated from Dendrobium venustum, possesses anti-migration activity and addressed its mechanism of action.MethodsThe cytotoxic and proliferative effects of phoyunnanin E on human non-small cell lung cancer-derived H460, H292, and A549 cells and human keratinocyte HaCaT cells were investigated by MTT assay. The effect of phoyunnanin E on EMT was evaluated by determining the colony formation and EMT markers. The migration and invasion of H460, H292, A549 and HaCaT cells was evaluated by wound healing assay and transwell invasion assay, respectively. EMT markers, integrins and migration-associated proteins were examined by western blot analysis.ResultsPhoyunnanin E at the concentrations of 5 and 10 μM, which are non-toxic to H460, H292, A549 and HaCaT cells showed good potential to inhibit the migratory activity of three types of human lung cancer cells. The anti-migration effect of phoyunnanin E was shown to relate to the suppressed EMT phenotypes, including growth in anchorage-independent condition, cell motility, and EMT-specific protein markers (N-cadherin, vimentin, slug, and snail). In addition to EMT suppression, we found that phoyunnanin E treatment with 5 and 10 μM could decrease the cellular level of integrin αv and integrin β3, these integrins are frequently up-regulated in highly metastatic tumor cells. We further characterized the regulatory proteins in cell migration and found that the cells treated with phoyunnanin E exhibited a significantly lower level of phosphorylated focal adhesion kinase (p-FAK) and phosphorylated ATP-dependent tyrosine kinase (p-AKT), and their downstream effectors (including Ras-related C3 botulinum (Rac-GTP); Cell division cycle 42 (Cdc42); and Ras homolog gene family, member A (Rho-GTP)) in comparison to those of the non-treated control.ConclusionsWe have determined for the first time that phoyunnanin E could inhibit the motility of lung cancer cells via the suppression of EMT and metastasis-related integrins. This new information could support further development of this compound for anti-metastasis approaches.

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Section: Discussionmentioning

confidence: 99%

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3

Petpiroon

Sritularak

Chanvorachote

2017

BMC Complement Altern Med

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“…WB showed that STYK1 over-expression downregulated the expression of epithelial marker E-cadherin while it upregulated mesenchymal protein markers (Figure 8C ). Previous studies showed that p38 MAPK signaling pathway was correlated with EMT and involved in cancer progression [ 14 , 15 ]. We next focused on the p38 MAPK pathways.…”

Section: Resultsmentioning

confidence: 99%

Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients

Chen

Bian

et al. 2017

Oncotarget

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Previous studies showed that aberrant Serine/threonine/tyrosine kinase 1 (STYK1, also known as NOK) or/and E-cadherin were involved in the progression of some types of human cancers. However, whether they contributed to the development of pancreatic cancer was unknown. Here, we investigated the prognostic significance of aberrant STYK1 and E-cadherin in pancreatic cancer. Our results showed that STYK1 expression increased while E-cadherin decreased in pancreatic cancer tissues compared with normal pancreas tissues. STYK1 level was positively correlated with lymph node metastasis and clinical stage in pancreatic cancer patients. E-cadherin expression was inversely correlated with STYK1 expression in pancreatic cancer tissue samples. Patients with high STYK1 and low E-cadherin expression had the worst prognosis. In addition, STYK1 knockdown in pancreatic cancer cell lines inhibited cell proliferation, enhanced cell apoptosis, induced cell cycle arrest, and prohibited cell migration, while STYK1 over-expression showed the opposite effects. Silencing STYK1 also increased E-cadherin expression and inhibited epithelial-to-mesenchymal transition (EMT) and p-p38 expression in vitro. Over-expression had showed the opposite trends, and treatment with p38 inhibitor, SB203580, could reverse the trends. Thus, STYK1 repressed E-cadherin expression and promoted EMT, mediated by p38 MAPK signaling pathway, which was the possible mechanism for STYK1-mediated pancreatic cancer cell proliferation and migration. In summary, our results showed that STYK1 might be a prognostic marker for pancreatic cancer patients and might be a novel strategy for the treatment of pancreatic cancer.

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“…The MAPK signaling pathway plays a role in EMT of the various kinds of epithelial cells and includes JNK, p38 MAPK, and ERK (Yang, Lee, & Shin, ; Zhang, Lian, & Liang, ; Zhang, Wang, & Fan, ). In order to assess the effect of mulberry leaves extracts on high glucose‐stimulated ERK1/2 activation, the expressions of phospho‐ERK1/2 were detected by western blot.…”

Section: Resultsmentioning

confidence: 99%

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

Zhu

et al. 2019

Phytotherapy Research

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Mulberry leaf was reported that it has antidiabetic activity, although the mechanisms underlying the function have not been fully elucidated. In the present study, the results of network pharmacology suggested that mulberry leaves could regulate key biological process in development of diabetes, and the process implicates multiple signaling pathways, such as JAK-STAT, MAPK, VEGF, PPAR, and Wnt. Then, the research in vitro indicated that mulberry leaves remarkably ameliorated high glucose-induced epithelial to mesenchymal transition, which was characterized with significant reduction of intracellular reactive oxygen species (ROS) levels as well as downregulation of NADPH oxidase subunits NOX1, NOX2, and NOX4, and it was found to be connected with the ERK1/2 signaling pathway in human tubular epithelial cells (HK-2). Moreover, the results of bioinformatics and the dual luciferase report showed that ZEB1 might be a target gene of miR-302a; decreased miR-302a and increased ZEB1 expressions could significantly promote epithelial to mesenchymal transition. However, mulberry leaves could reverse these modulations. Our results demonstrated that network pharmacology could provide a guidance role for traditional Chinese medicine research, and mulberry leaves could be of benefit in preventing high glucose-induced EMT in HK-2 cells, which proved that it was related to the upregulation of miR-302a by targeting ZEB1 and the inhibition of NADPH oxidase/ROS/ERK1/2 pathway.

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Glucocorticoids ameliorate TGF-β1-mediated epithelial-to-mesenchymal transition of airway epithelium through MAPK and Snail/Slug signaling pathways

Cited by 48 publications

References 44 publications

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3

Phoyunnanin E inhibits migration of non-small cell lung cancer cells via suppression of epithelial-to-mesenchymal transition and integrin αv and integrin β3

Aberrant expression of STYK1 and E-cadherin confer a poor prognosis for pancreatic cancer patients

The mechanism of mulberry leaves against renal tubular interstitial fibrosis through ERK1/2 signaling pathway was predicted by network pharmacology and validated in human tubular epithelial cells

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