TY  - JOUR
AU  - Sundararajan, Vignesh
AU  - Gengenbacher, Nicolas
AU  - Stemmler, Marc P
AU  - Kleemann, Julia A
AU  - Brabletz, Thomas
AU  - Brabletz, Simone
TI  - The ZEB1/miR-200c feedback loop regulates invasion via actin interacting proteins MYLK and TKS5.
JO  - OncoTarget
VL  - 6
IS  - 29
SN  - 1949-2553
CY  - [S.l.]
PB  - Impact Journals LLC
M1  - DKFZ-2017-03607
SP  - 27083 - 27096
PY  - 2015
AB  - Epithelial to mesenchymal transition (EMT) is a developmental process which is aberrantly activated during cancer invasion and metastasis. Elevated expression of EMT-inducers 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.
KW  - Actins (NLM Chemicals)
KW  - Adaptor Proteins, Vesicular Transport (NLM Chemicals)
KW  - CDH1 protein, human (NLM Chemicals)
KW  - Cadherins (NLM Chemicals)
KW  - Calcium-Binding Proteins (NLM Chemicals)
KW  - Homeodomain Proteins (NLM Chemicals)
KW  - MIRN200 microRNA, human (NLM Chemicals)
KW  - MicroRNAs (NLM Chemicals)
KW  - SH3PXD2A protein, human (NLM Chemicals)
KW  - Transcription Factors (NLM Chemicals)
KW  - ZEB1 protein, human (NLM Chemicals)
KW  - Zinc Finger E-box-Binding Homeobox 1 (NLM Chemicals)
KW  - MYLK protein, human (NLM Chemicals)
KW  - Myosin-Light-Chain Kinase (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:26334100
C2  - pmc:PMC4694975
DO  - DOI:10.18632/oncotarget.4807
UR  - https://inrepo02.dkfz.de/record/127584
ER  -