Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.4807
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dc.titleThe ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5
dc.contributor.authorSundararajan, V
dc.contributor.authorGengenbacher, N
dc.contributor.authorStemmler, M.P
dc.contributor.authorKleemann, J.A
dc.contributor.authorBrabletz, T
dc.contributor.authorBrabletz, S
dc.date.accessioned2020-10-20T03:15:21Z
dc.date.available2020-10-20T03:15:21Z
dc.date.issued2015
dc.identifier.citationSundararajan, V, Gengenbacher, N, Stemmler, M.P, Kleemann, J.A, Brabletz, T, Brabletz, S (2015). The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5. Oncotarget 6 (29) : 27083-27096. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.4807
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/177758
dc.description.abstractEpithelial to mesenchymal transition (EMT) is a developmental process which is aberrantly activated during cancer invasion and metastasis. Elevated expression of EMTinducers like ZEB1 enables tumor cells to detach from the primary tumor and invade into the surrounding tissue. The main antagonist of ZEB1 in controlling EMT is the microRNA-200 family that is reciprocally linked to ZEB1 in a double negative feedback loop. Here, we further elucidate how the ZEB1/miR-200 feedback loop controls invasion of tumor cells. The process of EMT is attended by major changes in the actin cytoskeleton. Via in silico screening of genes encoding for actin interacting proteins, we identified two novel targets of miR-200c - TKS5 and MYLK (MLCK). Co-expression of both genes with ZEB1 was observed in several cancer cell lines as well as in breast cancer patients and correlated with low miR-200c levels. Depletion of TKS5 or MYLK in breast cancer cells reduced their invasive potential and their ability to form invadopodia. Whereas TKS5 is known to be a major component, we could identify MYLK as a novel player in invadopodia formation. In summary, TKS5 and MYLK represent two mediators of invasive behavior of cancer cells that are regulated by the ZEB1/miR-200 feedback loop.
dc.publisherImpact Journals LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectactin
dc.subjectcell protein
dc.subjectmicroRNA 200c
dc.subjectmyosin light chain kinase
dc.subjectTKS5 protein
dc.subjecttranscription factor ZEB1
dc.subjectunclassified drug
dc.subjectactin
dc.subjectcadherin
dc.subjectcalcium binding protein
dc.subjectCDH1 protein, human
dc.subjecthomeodomain protein
dc.subjectmicroRNA
dc.subjectMIRN200 microRNA, human
dc.subjectMYLK protein, human
dc.subjectmyosin light chain kinase
dc.subjectSH3PXD2A protein, human
dc.subjecttranscription factor
dc.subjecttranscription factor ZEB1
dc.subjectvesicular transport adaptor protein
dc.subjectZEB1 protein, human
dc.subjectactin filament
dc.subjectArticle
dc.subjectbreast cancer cell line
dc.subjectcancer control
dc.subjectcancer patient
dc.subjectcell function
dc.subjectcomputer model
dc.subjectcontrolled study
dc.subjectepithelial mesenchymal transition
dc.subjectfeedback system
dc.subjectgene expression
dc.subjectgenetic screening
dc.subjecthuman
dc.subjecthuman cell
dc.subjectprotein depletion
dc.subjectprotein determination
dc.subjectprotein function
dc.subjectprotein protein interaction
dc.subjectprotein RNA binding
dc.subjecttumor invasion
dc.subjectbreast tumor
dc.subjectcytoskeleton
dc.subjectfemale
dc.subjectfluorescence microscopy
dc.subjectgene expression regulation
dc.subjectHEK293 cell line
dc.subjectmetabolism
dc.subjecttumor cell line
dc.subjecttumor invasion
dc.subjectActins
dc.subjectAdaptor Proteins, Vesicular Transport
dc.subjectBreast Neoplasms
dc.subjectCadherins
dc.subjectCalcium-Binding Proteins
dc.subjectCell Line, Tumor
dc.subjectCytoskeleton
dc.subjectEpithelial-Mesenchymal Transition
dc.subjectFemale
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectHEK293 Cells
dc.subjectHomeodomain Proteins
dc.subjectHumans
dc.subjectMicroRNAs
dc.subjectMicroscopy, Fluorescence
dc.subjectMyosin-Light-Chain Kinase
dc.subjectNeoplasm Invasiveness
dc.subjectTranscription Factors
dc.subjectZinc Finger E-box-Binding Homeobox 1
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.18632/oncotarget.4807
dc.description.sourcetitleOncotarget
dc.description.volume6
dc.description.issue29
dc.description.page27083-27096
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