scholarly journals A Comprehensive Analysis of Potential Gastric Cancer Prognostic Biomarker ITGBL1 Associated With Immune Infiltration and Epithelial–mesenchymal Transition

2021 ◽  
Author(s):  
Zhe Wang ◽  
Liu Fu ◽  
Junjie Zhang ◽  
Yanli Ge ◽  
Cheng Guo ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Immune Infiltration ◽  
Kaplan Meier ◽  
Bioinformatics Databases ◽  
Kaplan Meier Plotter ◽  
Tgf Β1

Abstract Background: Integrin, beta-like 1 (ITGBL1) is involved in a variety of human malignancies. However, the information on the involvement of ITGBL1 in gastric carcinoma (GC) is limited. Hence, this study aimed to further explore the functions and mechanisms of ITGBL1 in GC. Methods: First, multiple bioinformatics databases, including Oncomine, Timer, UALCAN, and Kaplan–Meier Plotter, were used to predict the expression level and prognostic value of ITGBL1, as well as its association with immune infiltration and epithelial–mesenchymal transition (EMT) in GC. Quantitative reverse transcription–polymerase chain reaction and immunohistochemical analysis were used to to detect the expression of ITGBL1 in both GC tissues and cells. Then, targeted silencing of ITGBL1 in GC cells was further to examine the biological functions of ITGBL1.Results: These databases revealed that ITGBL1 was overexpressed and affected the overall survival in GC. Besides, the expression of ITGBL1 positively correlated with immune-infiltrating cells and EMT-related markers. Subsequently, molecular biology experiments verified these predictions. In GC tissues and cells, ITGBL1 was notably overexpressed. Loss-of-function studies showed that the knockdown of ITGBL1 significantly suppressed migration and invasion but promoted apoptosis in MGC803 GC cells. Furthermore, the inhibition of ITGBL1 resulted in remarkably increased protein expression levels of cadherin 1 (CDH1), while the expression of Vimentin, Snail, and TGF-β1 was downregulated, indicating the initiation and progression of GC caused by ITGBL1 partly via inducing EMT. Conclusion: To sum up, the findings indicated that ITGBL1 acted as a valuable oncogenic factor in GC.

scholarly journals Overexpressed P75CUX1 promotes EMT in glioma infiltration by activating β-catenin

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Anqi Xu ◽  
Xizhao Wang ◽  
Jie Luo ◽  
Mingfeng Zhou ◽  
Renhui Yi ◽  
...  
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Tumor Grade ◽  
Prognostic Indicator ◽  
Migration And Invasion ◽  
Poor Overall Survival ◽  
Mesenchymal Transition ◽  
Kaplan Meier ◽  
Homeobox Protein

AbstractThe homeobox protein cut-like 1 (CUX1) comprises three isoforms and has been shown to be involved in the development of various types of malignancies. However, the expression and role of the CUX1 isoforms in glioma remain unclear. Herein, we first identified that P75CUX1 isoform exhibited consistent expression among three isoforms in glioma with specifically designed antibodies to identify all CUX1 isoforms. Moreover, a significantly higher expression of P75CUX1 was found in glioma compared with non-tumor brain (NB) tissues, analyzed with western blot and immunohistochemistry, and the expression level of P75CUX1 was positively associated with tumor grade. In addition, Kaplan–Meier survival analysis indicated that P75CUX1 could serve as an independent prognostic indicator to identify glioma patients with poor overall survival. Furthermore, CUX1 knockdown suppressed migration and invasion of glioma cells both in vitro and in vivo. Mechanistically, this study found that P75CUX1 regulated epithelial–mesenchymal transition (EMT) process mediated via β-catenin, and CUX1/β-catenin/EMT is a novel signaling cascade mediating the infiltration of glioma. Besides, CUX1 was verified to promote the progression of glioma via multiple other signaling pathways, such as Hippo and PI3K/AKT. In conclusion, we suggested that P75CUX1 could serve as a potential prognostic indicator as well as a novel treatment target in malignant glioma.

Neuropilin 1 modulates TGF-β1-induced epithelial–mesenchymal transition in non-small cell lung cancer

2019 ◽  
Author(s):  
Zongli Ding ◽  
Wenwen Du ◽  
Zhe Lei ◽  
Yang Zhang ◽  
Jianjie Zhu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Wound Healing ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Migration And Invasion ◽  
Wound Healing Assay ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Tgf Β1

Abstract Background: TGF-β1 signaling is a potent inducer of epithelial-mesenchymal transition (EMT) in various cancers. Our previous study has indicated that NRP1 was significantly up-regulated and acted as a vital promoter in the metastasis of non-small cell lung cancer (NSCLC). However, the function of NRP1 in regulation of TGF-β1-induced EMT and NSCLC cell migration and invasion remained unclear. Methods: The differential expression level of NRP1 was determined by RT-PCR analysis in human tissue samples with or without lymph node metastasis. Transwell assay and wound healing assay were conducted to determine cell ability of migration. Lentivirus-mediated stable knockdown and overexpression of NRP1 cell lines were constructed. Exogenous TGF-β1 stimulation, SIS3 treatment, western blot analysis and in vivo metastatic model were utilized to clarify the underlying regulatory mechanism. Results: Increased expression of NRP1 was found in metastatic NSCLC tissues and can promote NSCLC metastasis in vivo. Transwell assays, wound healing assay and western blot analysis showed that knockdown of NRP1 significantly inhibited TGF-β1-mediated EMT and migratory and invasive capabilities of A549 and H226 cells. Furthermore, overexpression of NRP1 could weak the decreased migratory and invasive capabilities with SIS3 treatment. Co-IP data showed that NRP1 can interact with TGFβRⅡ to induce EMT. Conclusion: This is the first time to report that NRP1 can modulate TGF-β1-induced EMT and cell migration and invasion in NSCLC.

scholarly journals FOXM1 Drives Epithelial-Mesenchymal Transition Program Through E-Cadherin Promoter Biding Ability in Non-Small-Cell Lung Cancer Cells

2021 ◽  
Author(s):  
Ling Wang ◽  
Lin Xiaolan ◽  
ZongSheng Jiang ◽  
Yanzi Sun ◽  
Yixuan Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Enzyme Assay ◽  
Epithelial Mesenchymal Transition ◽  
Small Cell ◽  
Migration And Invasion ◽  
Small Cell Lung ◽  
Mesenchymal Transition ◽  
Reporter Enzyme ◽  
Tgf Β1 ◽  
E Cadherin

Abstract Background: Forkhead box (FOX) gene family plays a critical role in regulating Epithelial-mesenchymal transition (EMT) program, and in which, FOXM1 can mediate multiple malignant process in many type of tumor cells. However, the modulate functions of FOXM1 on EMT in non-small-cell lung cancer (NSCLC) cells, especially the transcriptional function on E-cadherin coding gene CDH1 remains unclear. This article mainly focuses on FOXM1, exploring its mechanism in regulating EMT of NSCLC cells, and FOXM1 inhibitor thiostrepton’s effects in EMT intervention. Methods: Morphological changes of overexpressed cells were observed by HE staining. The effects of scratch test, Transwell chamber test and Western-blot analysis on cell migration and invasion ability and the expression of EMT-related markers were analyzed. Dual luciferin reporter enzyme assay and nuclear transcription factor immunoprecipitation assay (ChIP, immunofluorescence) revealed the transcriptional regulation of FOXM1 on EMT markers. MTT assay and clone formation assay were used to determine the effect of thiomycin on the viability of NSCLC cells and the ability of cell clone formation.Rusults: After overexpression of FOXM1, the cells showed intermediate epithelial-mesenchymal morphology, but not complete mesenchymal morphology, and their migration and invasion abilities were enhanced. The protein expression levels of N-cadherin,Snail1 and Vimentin were increased, while the expression levels of E-cadherin were decreased. On the contrary, knockdown of FOXM1 expression showed the opposite result. The double luciferin reporter enzyme assay showed that FOXM1 inhibited the luciferin reporter vector CDH1-2000-promoter. ChIP results confirmed that FOXM1 could bind endogenous to CDH1 gene promoter. In cells overexpressing FOXM1, knockdown of Snail further promotes FOXM1-mediated CDH1 transcription. MTT results and clone formation experiments showed that thiomycin had inhibitory effect on the proliferation of NSCLC cells. Morphological observation, cell migration assay and Transwell chamber assay showed that streptotin inhibited TGF-β1-induced enhanced cell migration and invasion. Western-blot analysis showed that thiomycin down-regulated the expression of FOXM1, N-cadherin, Snail, and Vimentin induced by TGF-β1, while blocking the expression of E-cadherin induced by TGF-β1 decreased.Conclusion: FOXM1 can directly bind to the promoter of E-cadherin encoding gene, and can indirectly inhibit E-cadherin expression by stimulating Snail. Overexpression of FOXM1 can promote EMT progression in NSCLC cells. Therefore, down-regulation of FOXM1 can inhibit this process. In addition, thiostrepton, a FOXM1 inhibitor, blocked proliferation, colony formation, and EMT progression in NSCLC cells.

scholarly journals SQSTM1/p62 in Intrahepatic Cholangiocarcinoma Promotes Tumor Progression Via Epithelial-Mesenchymal Transition and Mitochondrial Function Maintenance

2021 ◽  
Author(s):  
Jiafeng Chen ◽  
Zheng Gao ◽  
Xiaogang Li ◽  
Yinghong Shi ◽  
Zheng Tang ◽  
...  
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Mitochondrial Function ◽  
Epithelial Mesenchymal Transition ◽  
Immunohistochemical Analysis ◽  
Vital Role ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Consumption Rates ◽  
Invasive Capacity

Abstract Background: SQSTM1/p62, as a selective autophagy receptor, regulates multiple signaling pathways participating in the initiation and progression of tumors. Since metastasis is still a main cause for intrahepatic cholangiocarcinoma (ICC)-associated mortality, this study aimed to explore the mechanism of p62 promoting progression of ICC.Methods: Western blotting and immunohistochemical analysis were conducted to detect the expression level of protein p62 in ICC tissues. Subsequently, loss of function experiments was applied to define the role of p62 in the progression of ICC in vitro and in vivo. Mitochondrial function and mitophagy was evaluated by measuring oxygen consumption rates (OCR) and immunofluorescence detection respectively.Results: Here we identified expression of p62 was significantly upregulated in ICC specimens compared to normal tissue. And we further illustrated that p62 expression was positively correlated with lymph-node metastasis and poor prognosis. Loss of function assays revealed that p62 not only promoted ICC cells proliferation, migration and invasive capacity in vitro, but also induced lung metastasis in xenograft mouse model. Mechanistically, high expression of p62 induced epithelial-mesenchymal transition (EMT) with upregulation of Snail1, Vimentin and down-regulation of E-Cadherin. Moreover, OCR assays and immunofluorescence cell staining demonstrated that the autophagy-dependent function of p62 may play a vital role in maintaining mitochondrial function of ICC by mitophagy.Conclusions: These data provide new evidence and feasible mechanism that abundant p62 expression promote ICC progression, suggesting a promising therapeutic target for anti-metastatic strategies in ICC patients.

scholarly journals TGFβ1-induced cell motility is mediated through Cten in colorectal cancer

2018 ◽  
Author(s):  
Abdulaziz Asiri ◽  
Teresa Pereira Raposo ◽  
Abdulaziz Alfahed ◽  
Mohammad Ilyas
Keyword(s):  
Colorectal Cancer ◽  
Cell Motility ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Growth Factor Beta ◽  
Emt Markers ◽  
Tgf Β1

ABSTRACTCten is a tensin which promotes epithelial-mesenchymal transition (EMT) and cell motility. The precise mechanisms regulating Cten are unknown, although Cten could be regulated by several cytokines and growth factors. Since Transforming growth factor beta 1 (TGF-β1) regulates integrin function and promotes EMT / cell motility, we investigated whether this happens through Cten signalling in colorectal cancer (CRC).TGF-β1 signalling was modulated by either stimulation or knockdown in the CRC cell lines SW620 and HCT116. The effect of this modulation on expression of Cten, EMT markers and cellular function was tested. Cten role as a direct mediator of TGF-β1 signalling was investigated in a CRC cell line with a deleted Cten gene (SW620ΔCten).When TGF-β1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers. Cell migration and invasion were significantly increased following TGF-β1 stimulation and lost by TGF-β1 knockdown. TGF-β1 stimulation in SW620ΔCten resulted in selective loss of the effect of TGF-β1 signalling on EMT and cell motility whilst the stimulatory effect on cell proliferation was retained.These data suggested Cten may play an essential role in mediating TGF-β1-induced EMT and cell motility and may play a role in metastasis in CRC.

LncRNA ZFAS1, as a poor prognostic indicator, promotes cell proliferation and epithelial–mesenchymal transition in endometrial carcinoma

2020 ◽  
Author(s):  
Yanan Sun ◽  
Xuan Gao ◽  
Peiling Li ◽  
Ling Song ◽  
Lei Shi
Keyword(s):  
Endometrial Carcinoma ◽  
Noncoding Rna ◽  
Epithelial Mesenchymal Transition ◽  
Histological Grade ◽  
Myometrial Invasion ◽  
Migration And Invasion ◽  
Factor X ◽  
Loss Of Function ◽  
Mesenchymal Transition ◽  
Gynecology And Obstetrics

Background: Long noncoding RNA Zinc finger nuclear transcription factor, X-box binding 1-type containing 1 antisense RNA 1 (ZFAS1) has been reported to be an oncogene in various tumors. However, the role of ZFAS1 in endometrial carcinoma (EC) are not fully determined. Methods & results: Here, we found ZFAS1 expression was significantly upregulated in EC patients, which was significantly associated with International Federation of Gynecology and Obstetrics stage, histological grade, myometrial invasion and poor prognosis. The loss-of-function assays showed that knockdown of ZFAS1 significantly suppressed the proliferation, G1/S transition, migration and invasion in EC cells. Moreover, knockdown of ZFAS1 obviously downregulated the expression of CDK4, Cyclin D1 and N-cadherin, but upregulated E-cadherin expression. Conclusion: Collectively, these results suggest that ZFAS1 might be used as potential therapeutic targets for EC treatment.

scholarly journals Babao Dan inhibits the migration and invasion of gastric cancer cells by suppressing epithelial–mesenchymal transition through the TGF-β/Smad pathway

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092559 ◽  
Author(s):  
Jianxin Liu ◽  
Yongan Chen ◽  
Zhiyun Cao ◽  
Bin Guan ◽  
Jun Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Cell Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Live Cell ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Ratio ◽  
Tgf Β1

Objective To investigate the anti-metastatic effects of Babao Dan (BBD) on gastric cancer (GC) cells (AGS and MGC80-3) and explore the underlying molecular mechanisms by which it inhibits epithelial–mesenchymal transition (EMT). Methods AGS and MGC80-3 cells were treated with BBD. In addition, cells were treated with the EMT inducer transforming growth factor-β1 (TGF-β1). Cell viability was determined using the MTT assay, and the live cell ratio was calculated via cell counting. Cell invasion and migration were evaluated using the Transwell assay. Western blotting was performed to measure the protein expression of EMT biomarkers and related genes. Results BBD inhibited the viability, migration, and invasion of AGS and MGC80-3 cells, but it did not reduce the live cell ratio. Furthermore, BBD inhibited the expression of N-cadherin, vimentin, zinc finger E-box binding homeobox (ZEB)1, ZEB2, Twist1, matrix metalloproteinase (MMP)2, MMP9, TGF-β1, and p-Smad2/3, whereas E-cadherin expression was increased in AGS and MGC80-3 cells to different degrees. Using a GC cell model of EMT induced by TGF-β1, we proved that BBD inhibited p-Smad2/3 and N-cadherin expression, cell migration, and cell invasion. Conclusion BBD suppressed cell migration and invasion by inhibiting TGF-β–induced EMT and inactivating TGF-β/Smad signaling in GC cells.

scholarly journals RhoA-Dependent HGF and c-Met Mediate Gas6-Induced Inhibition of Epithelial–Mesenchymal Transition, Migration, and Invasion of Lung Alveolar Epithelial Cells

Biomolecules ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 565 ◽  
Author(s):  
Jung ◽  
Yang ◽  
Kim ◽  
Lee ◽  
Kim ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Epithelial Mesenchymal Transition ◽  
Rho Kinase ◽  
Alveolar Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Alveolar Epithelial ◽  
Tgf Β1

Previously, we demonstrated that growth arrest-specific protein 6 (Gas6)/Axl or Mer signaling inhibited the transforming growth factor (TGF)-β1-induced epithelial–mesenchymal transition (EMT) in lung epithelial cells. Hepatocyte growth factor (HGF) has also been shown to inhibit TGF-β1-induced changes in EMT markers. Here, we examined whether Gas6 signaling can induce the production of HGF and c-Met in lung alveolar epithelial cells to mediate the inhibition of EMT and to inhibit the migration and invasion of epithelial cells. The inhibition of the RhoA/Rho kinase pathway, using either a RhoA-targeted small interfering RNA (siRNA) or the Rho kinase pharmacologic inhibitor Y27362, prevented the inhibition of TGF-β1-induced EMT in LA-4 cells and primary alveolar type II (AT II) epithelial cells. The c-Met antagonist PHA-665752 also blocked the anti-EMT effects associated with Gas6. Moreover, treatment with Y27362 or PHA-665752 prevented the Gas6-mediated inhibition of TGF-β1-induced migration and invasion. Our data provided evidence that the RhoA-dependent production of HGF and c-Met mediated the Gas6-induced inhibition of EMT, migration and invasion in lung alveolar epithelial cells. Thus, Gas6/Axl and Mer/RhoA signaling may be necessary for the maintenance of homeostasis in the alveolar epithelium, via HGF and c-Met.

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