scholarly journals PPTS Inhibits the TGF-β1-Induced Epithelial-Mesenchymal Transition in Human Colorectal Cancer SW480 Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Ling Zhang ◽  
Abid Naeem ◽  
Shaofeng Wei ◽  
Zexie Li ◽  
Zhenzhong Zang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Research Work ◽  
Human Colorectal Cancer ◽  
Migration Ability ◽  
Triterpenoid Saponins ◽  
Mesenchymal Transition ◽  
Sw480 Cells

The current study investigates the inhibitory effects of Pulsatilla pentacyclic triterpenoid saponins extract (PPTS) on epithelial-mesenchymal transition (EMT) triggered by the transforming growth factor-β1 (TGF-β1) in human colorectal cancer SW480 cell line, further illustrates the possible mechanism of PPTS inhibition of growth and invasion from the perspective of EMT, and provides new theoretical support for the treatment of tumor by Chinese medicine. The SW480 cells were treated in groups: blank control, TGF-β1 (10 ng/mL), and varying concentrations of PPTS cotreated with TGF-β1-induced (10 ng/mL) groups. CCK8 was used to detect cell viability; transwell was applied to detect invasion ability, cell migration ability was also determined, ELISA and RT-qPCR were utilized for the determination of CYP3A, CYP2C9, CYP2C19, N-cadherin, and MMP-9 expression. Flow cytometry detection was applied to detect cell cycle and apoptosis. The results obtained have shown that PPTS can significantly inhibit the invasion and migration of tumors in SW480 cells and can also block the S phase in the cell cycle but may produce cytotoxicity in higher doses. The present research work provides substantial evidence that PPTS has a significant inhibitory effect on TGF-β1-induced EMT in SW480 cells and it also promotes apoptosis.

scholarly journals Calcium Channel Protein ORAI1 Mediates TGF-β Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingjie Kang ◽  
Xudong Peng ◽  
Xiangshu Li ◽  
Denghua Hu ◽  
Guangxu Wen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Calcium Channel ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Sw480 Cells ◽  
Sw620 Cells ◽  
Tgf Β1

Accumulating evidence suggested that calcium release-activated calcium modulator 1(ORAI1), a key calcium channel pore-forming protein-mediated store-operated Ca2+ entry (SOCE), is associated with human cancer. However, its role in colorectal cancer (CRC) progression has not been well studied. Epithelial-mesenchymal transition (EMT) is a multistep process that occurs during the progression of cancers and is necessary for metastasis of epithelial cancer. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that has been shown to induce EMT. In this study, we are aimed at exploring the effects of ORAI1 on TGF-β1-induced EMT process in CRC cells. Herein, we confirmed ORAI1 expression was higher in CRC tissues than in adjacent non-cancerous tissues by using immunohistochemical staining and Western blot analysis. Higher ORAI1 expression was associated with more advanced clinical stage, higher incidence of metastasis and shorter overall survival. We compared ORAI1 expression in SW480 and SW620 cells, two CRC cell lines with the same genetic background, but different metastatic potential. We found ORAI1 expression was significantly higher in SW620 cells which exhibited higher EMT characteristics. Furthermore, knockdown of ORAI1 suppressed the EMT of SW620 Cells. After induced the EMT process in SW480 cells with TGF-β1, we found treatment of TGF-β1 showed a significant increase in cell migration along with the loss of E-cadherin and an increase in N-cadherin and Vimentin protein levels. Also, TGF-β1 treatment increased ORAI1 expression and was closely associated with the increase of SOCE. Silencing ORAI1 significantly suppressed Ca2+ entry, reversed the changes of EMT-relevant marks expression induced by TGF-β1, and inhibited TGF-β1-mediated calpain activation and cell migration. Finally, we blocked SOCE with 2-APB (2-Aminoethyl diphenylborinate), a pharmacological inhibitor. Interestingly, 2-APB and sh-ORAI1 both exhibited similar inhibition effects to the SW480 cells. In conclusion, our results demonstrated that ORAI1 could mediate TGF-β-Induced EMT by promoting Ca2+ entry and calpain activity in Colorectal Cancer Cells.

scholarly journals SMAD4 mutations do not preclude epithelial–mesenchymal transition in colorectal cancer

Oncogene ◽  
2021 ◽  
Author(s):  
Patrick Frey ◽  
Antoine Devisme ◽  
Katja Rose ◽  
Monika Schrempp ◽  
Vivien Freihen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Morphological Changes ◽  
Expression Patterns ◽  
Human Tumor ◽  
Marker Genes ◽  
Mesenchymal Transition ◽  
Gene Regulatory

AbstractTransforming growth factor beta (TGFβ) superfamily signaling is a prime inducer of epithelial-mesenchymal transitions (EMT) that foster cancer cell invasion and metastasis, a major cause of cancer-related deaths. Yet, TGFβ signaling is frequently inactivated in human tumor entities including colorectal cancer (CRC) and pancreatic adenocarcinoma (PAAD) with a high proportion of mutations incapacitating SMAD4, which codes for a transcription factor (TF) central to canonical TGFβ and bone morphogenetic protein (BMP) signaling. Beyond its role in initiating EMT, SMAD4 was reported to crucially contribute to subsequent gene regulatory events during EMT execution. It is therefore widely assumed that SMAD4-mutant (SMAD4mut) cancer cells are unable to undergo EMT. Here, we scrutinized this notion and probed for potential SMAD4-independent EMT execution using SMAD4mut CRC cell lines. We show that SMAD4mut cells exhibit morphological changes, become invasive, and regulate EMT marker genes upon induction of the EMT-TF SNAIL1. Furthermore, SNAIL1-induced EMT in SMAD4mut cells was found to be entirely independent of TGFβ/BMP receptor activity. Global assessment of the SNAIL1-dependent transcriptome confirmed the manifestation of an EMT gene regulatory program in SMAD4mut cells highly related to established EMT signatures. Finally, analyses of human tumor transcriptomes showed that SMAD4 mutations are not underrepresented in mesenchymal tumor samples and that expression patterns of EMT-associated genes are similar in SMAD4mut and SMAD4 wild-type (SMAD4wt) cases. Altogether, our findings suggest that alternative TFs take over the gene regulatory functions of SMAD4 downstream of EMT-TFs, arguing for considerable plasticity of gene regulatory networks operating in EMT execution. Further, they establish that EMT is not categorically precluded in SMAD4mut tumors, which is relevant for their diagnostic and therapeutic evaluation.

scholarly journals LncRNA HOXB-AS3 Promotes Proliferation, Migration, Invasion, and Epithelial-Mesenchymal Transition of Gallbladder Cancer Cells by Activating the MEK/ERK Pathway

2022 ◽  
Author(s):  
Jiayan Wu ◽  
Hongquan Zhu ◽  
Jiandong Yu ◽  
Zhiping Chen ◽  
Zeyu Lin ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Migration ◽  
Cell Viability ◽  
Gallbladder Cancer ◽  
Cell Apoptosis ◽  
Epithelial Mesenchymal Transition ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Migration Ability ◽  
Mesenchymal Transition

Abstract OBJECTIVE: Long non-coding RNA HOXB-AS3 has been implicated in tumor progression in a variety of carcinomas. However, its biological role in gallbladder cancer (GBC) is unknown. The biological function and underlying mechanism of the lncRNA HOXB-AS3 for GBC were investigated in this study.MATERIALS AND METHODS: To investigate the function of lncRNA HOXB-AS3 in GBC, the level of lncRNA HOXB-AS3 in GBC cells was detected by quantitative reverse-transcription polymerase chain reaction. The cell viability was tested by cell counting kit-8 assay and colony formation assay. Flow cytometry was performed to investigate cell apoptosis and cell cycle. In addition, cell migration ability was assessed by wound healing assay and cell invasion ability by transwell invasion assay. RESULTS: It was found that HOXB-AS3 was obviously elevated in GBC tissues and cells. However, inhibition of HOXB-AS3 could depress NOZ and GBC-SD cell viability as well as induce cell apoptosis. Also, the gallbladder cancer cell cycle was blocked in the G1 phase. Meanwhile, NOZ and GBC-SD cell migration, invasion, and epithelial-mesenchymal transition were obviously suppressed by knockdown of HOXB-AS3. What is more, we found that HOXB-AS3 might promote gallbladder progress by activating the MEK/ERK pathway.CONCLUSION: The results show that lncRNA HOXB-AS3 serves as a key regulator in GBC progression, which provides a new treatment strategy for GBC.

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