RRC ID 47320
Author Ko C, Kim YG, Le TP, Choi KW.
Title Twinstar/cofilin is required for regulation of epithelial integrity and tissue growth in Drosophila.
Journal Oncogene
Abstract Regulation of actin assembly and depolymerization is important for the organization of epithelia. Recent studies have shown that the actin-capping proteins are required to prevent cell extrusion and inappropriate activation of Yorkie (Yki) activity in Drosophila, implicating the importance of actin regulation for epithelial integrity and Yki-dependent tissue growth. However, the role of Twinstar (Tsr), the Drosophila homolog for cofilin/actin depolymerization factor (ADF), in epithelial integrity and Hippo signaling is unknown. Here we demonstrate that reduction of Tsr by RNA interference (RNAi) or mutant clones in wing imaginal disc induces not only F-actin accumulation but also ectopic expression of Wingless (Wg) and Yki target gene expanded (ex). Knockdown of Yki in Tsr-depleted cells reduced the level of ectopic Wg expression. Reduced Tsr also led to downregulation of cell junction proteins and extrusion of affected cells from the basal part of the epithelium. Rho GTPase 1 was upregulated in Tsr-depleted tissue, supporting the Tsr function in the inhibition of cell extrusion from the epithelium. Tsr is also required for blocking cell death and c-Jun N-terminal kinase (JNK) signaling. Ectopic JNK activation induced caspase activation but did not cause cell extrusion. Further, the invasiveness of Tsr-depleted cells was not suppressed by inhibition of cell death or JNK signaling. In contrast, Yki upregulation was significantly suppressed by cell death inhibition. Taken together, our data suggest that Tsr is required for cell survival and tissue growth by regulating JNK and Yki signaling while maintaining the epithelial integrity by controlling cell junctions. This study provides an insight into potential roles of ADF/cofilin in invasive cell migration and tumor suppression in higher animals.
Volume 35(39)
Pages 5144-54
Published 2016-9-29
DOI 10.1038/onc.2016.46
PII onc201646
PMID 27041568
MeSH Actins / genetics Actins / metabolism Animals Cell Movement / genetics* Drosophila Proteins / genetics* Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Epithelium / growth & development* Epithelium / metabolism Gene Expression Regulation, Developmental Imaginal Discs / growth & development Imaginal Discs / metabolism MAP Kinase Signaling System / genetics Microfilament Proteins / genetics* Nuclear Proteins / genetics RNA Interference Signal Transduction / genetics Trans-Activators / genetics Wings, Animal / growth & development Wnt1 Protein / genetics YAP-Signaling Proteins rho GTP-Binding Proteins / genetics
IF 7.971
Times Cited 6