scholarly journals Hic-5 promotes invadopodia formation and invasion during TGF-β–induced epithelial–mesenchymal transition

2012 ◽  
Vol 197 (3) ◽  
pp. 421-437 ◽  
Author(s):  
Jeanine Pignatelli ◽  
David A. Tumbarello ◽  
Ronald P. Schmidt ◽  
Christopher E. Turner
Keyword(s):  
Cell Migration ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Ectopic Expression ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Matrix Degradation ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Invadopodia Formation

Transforming growth factor β (TGF-β)–stimulated epithelial–mesenchymal transition (EMT) is an important developmental process that has also been implicated in increased cell invasion and metastatic potential of cancer cells. Expression of the focal adhesion protein Hic-5 has been shown to be up-regulated in epithelial cells in response to TGF-β. Herein, we demonstrate that TGF-β–induced Hic-5 up-regulation or ectopic expression of Hic-5 in normal MCF10A cells promoted increased extracellular matrix degradation and invasion through the formation of invadopodia. Hic-5 was tyrosine phosphorylated in an Src-dependent manner after TGF-β stimulation, and inhibition of Src activity or overexpression of a Y38/60F nonphosphorylatable mutant of Hic-5 inhibited matrix degradation and invasion. RhoC, but not RhoA, was also required for TGF-β– and Hic-5–induced matrix degradation. Hic-5 also induced matrix degradation, cell migration, and invasion in the absence of TGF-β via Rac1 regulation of p38 MAPK. These data identify Hic-5 as a critical mediator of TGF-β–stimulated invadopodia formation, cell migration, and invasion.

Visfatin facilitates gastric cancer malignancy by targeting snai1 via the NF-κB signaling

2021 ◽  
pp. 096032712110061
Author(s):  
D Cao ◽  
L Chu ◽  
Z Xu ◽  
J Gong ◽  
R Deng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Migration ◽  
Western Blot ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Protein Levels

Background: Visfatin acts as an oncogenic factor in numerous tumors through a variety of cellular processes. Visfatin has been revealed to promote cell migration and invasion in gastric cancer (GC). Snai1 is a well-known regulator of EMT process in cancers. However, the relationship between visfatin and snai1 in GC remains unclear. The current study aimed to explore the role of visfatin in GC. Methods: The RT-qPCR and western blot analysis were used to measure RNA and protein levels, respectively. The cell migration and invasion were tested by Trans-well assays and western blot analysis. Results: Visfatin showed upregulation in GC cells. Additionally, Visfatin with increasing concentration facilitated epithelial-mesenchymal transition (EMT) process by increasing E-cadherin and reducing N-cadherin and Vimentin protein levels in GC cells. Moreover, endogenous overexpression and knockdown of visfatin promoted and inhibited migratory and invasive abilities of GC cells, respectively. Then, we found that snai1 protein level was positively regulated by visfatin in GC cells. In addition, visfatin activated the NF-κB signaling to modulate snai1 protein expression. Furthermore, the silencing of snai1 counteracted the promotive impact of visfatin on cell migration, invasion and EMT process in GC. Conclusion: Visfatin facilitates cell migration, invasion and EMT process by targeting snai1 via the NF-κB signaling, which provides a potential insight for the treatment of GC.

scholarly journals MicroRNA-155 Is Regulated by the Transforming Growth Factor β/Smad Pathway and Contributes to Epithelial Cell Plasticity by Targeting RhoA

2008 ◽  
Vol 28 (22) ◽  
pp. 6773-6784 ◽  
Author(s):  
William Kong ◽  
Hua Yang ◽  
Lili He ◽  
Jian-jun Zhao ◽  
Domenico Coppola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Growth Factor ◽  
Tight Junction ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Migration And Invasion ◽  
Advanced Malignancy ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

ABSTRACT Transforming growth factor β (TGF-β) signaling facilitates metastasis in advanced malignancy. While a number of protein-encoding genes are known to be involved in this process, information on the role of microRNAs (miRNAs) in TGF-β-induced cell migration and invasion is still limited. By hybridizing a 515-miRNA oligonucleotide-based microarray library, a total of 28 miRNAs were found to be significantly deregulated in TGF-β-treated normal murine mammary gland (NMuMG) epithelial cells but not Smad4 knockdown NMuMG cells. Among upregulated miRNAs, miR-155 was the most significantly elevated miRNA. TGF-β induces miR-155 expression and promoter activity through Smad4. The knockdown of miR-155 suppressed TGF-β-induced epithelial-mesenchymal transition (EMT) and tight junction dissolution, as well as cell migration and invasion. Further, the ectopic expression of miR-155 reduced RhoA protein and disrupted tight junction formation. Reintroducing RhoA cDNA without the 3′ untranslated region largely reversed the phenotype induced by miR-155 and TGF-β. In addition, elevated levels of miR-155 were frequently detected in invasive breast cancer tissues. These data suggest that miR-155 may play an important role in TGF-β-induced EMT and cell migration and invasion by targeting RhoA and indicate that it is a potential therapeutic target for breast cancer intervention.

scholarly journals Visfatin promotes osteosarcoma cell migration and invasion via induction of epithelial-mesenchymal transition

2015 ◽  
Vol 34 (2) ◽  
pp. 987-994 ◽  
Author(s):  
GONG CHENG ◽  
CHANGYING LIU ◽  
XIUJIANG SUN ◽  
LEI ZHANG ◽  
LIFANG LIU ◽  
...  
Keyword(s):  
Cell Migration ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Osteosarcoma Cell ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion

scholarly journals MicroRNA-138 suppresses epithelial–mesenchymal transition in squamous cell carcinoma cell lines

2011 ◽  
Vol 440 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Xiqiang Liu ◽  
Cheng Wang ◽  
Zujian Chen ◽  
Yi Jin ◽  
Yun Wang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Migration ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Down Regulation ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion ◽  
Direct Targeting

Down-regulation of miR-138 (microRNA-138) has been frequently observed in various cancers, including HNSCC (head and neck squamous cell carcinoma). Our previous studies suggest that down-regulation of miR-138 is associated with mesenchymal-like cell morphology and enhanced cell migration and invasion. In the present study, we demonstrated that these miR-138-induced changes were accompanied by marked reduction in E-cad (E-cadherin) expression and enhanced Vim (vimentin) expression, characteristics of EMT (epithelial–mesenchymal transition). On the basis of a combined experimental and bioinformatics analysis, we identified a number of miR-138 target genes that are associated with EMT, including VIM, ZEB2 (zinc finger E-box-binding homeobox 2) and EZH2 (enhancer of zeste homologue 2). Direct targeting of miR-138 to specific sequences located in the mRNAs of the VIM, ZEB2 and EZH2 genes was confirmed using luciferase reporter gene assays. Our functional analyses (knock-in and knock-down) demonstrated that miR-138 regulates the EMT via three distinct pathways: (i) direct targeting of VIM mRNA and controlling the expression of VIM at a post-transcriptional level, (ii) targeting the transcriptional repressors (ZEB2) which in turn regulating the transcription activity of the E-cad gene, and (iii) targeting the epigenetic regulator EZH2 which in turn modulates its gene silencing effects on the downstream genes including E-cad. These results, together with our previously observed miR-138 effects on cell migration and invasion through targeting RhoC (Rho-related GTP-binding protein C) and ROCK2 (Rho-associated, coiled-coil-containing protein kinase 2) concurrently, suggest that miR-138 is a multi-functional molecular regulator and plays major roles in EMT and in HNSCC progression.

scholarly journals FHOD1, a Formin Upregulated in Epithelial-Mesenchymal Transition, Participates in Cancer Cell Migration and Invasion

PLoS ONE ◽  
2013 ◽  
Vol 8 (9) ◽  
pp. e74923 ◽  
Author(s):  
Maria Gardberg ◽  
Katja Kaipio ◽  
Laura Lehtinen ◽  
Piia Mikkonen ◽  
Vanina D. Heuser ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cancer Cell ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Cancer Cell Migration ◽  
Mesenchymal Transition ◽  
Cell Migration And Invasion
Sign in / Sign up

Export Citation Format

Share Document