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https://doi.org/10.18632/oncotarget.4807
Title: | The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5 | Authors: | Sundararajan, V Gengenbacher, N Stemmler, M.P Kleemann, J.A Brabletz, T Brabletz, S |
Keywords: | actin cell protein microRNA 200c myosin light chain kinase TKS5 protein transcription factor ZEB1 unclassified drug actin cadherin calcium binding protein CDH1 protein, human homeodomain protein microRNA MIRN200 microRNA, human MYLK protein, human myosin light chain kinase SH3PXD2A protein, human transcription factor transcription factor ZEB1 vesicular transport adaptor protein ZEB1 protein, human actin filament Article breast cancer cell line cancer control cancer patient cell function computer model controlled study epithelial mesenchymal transition feedback system gene expression genetic screening human human cell protein depletion protein determination protein function protein protein interaction protein RNA binding tumor invasion breast tumor cytoskeleton female fluorescence microscopy gene expression regulation HEK293 cell line metabolism tumor cell line tumor invasion Actins Adaptor Proteins, Vesicular Transport Breast Neoplasms Cadherins Calcium-Binding Proteins Cell Line, Tumor Cytoskeleton Epithelial-Mesenchymal Transition Female Gene Expression Regulation, Neoplastic HEK293 Cells Homeodomain Proteins Humans MicroRNAs Microscopy, Fluorescence Myosin-Light-Chain Kinase Neoplasm Invasiveness Transcription Factors Zinc Finger E-box-Binding Homeobox 1 |
Issue Date: | 2015 | Publisher: | Impact Journals LLC | Citation: | Sundararajan, 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 | Rights: | Attribution 4.0 International | Abstract: | Epithelial 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. | Source Title: | Oncotarget | URI: | https://scholarbank.nus.edu.sg/handle/10635/177758 | ISSN: | 19492553 | DOI: | 10.18632/oncotarget.4807 | Rights: | Attribution 4.0 International |
Appears in Collections: | Staff Publications Elements |
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