PMID- 29498307 OWN - NLM STAT- MEDLINE DCOM- 20181217 LR - 20211204 IS - 1543-5180 (Electronic) IS - 1543-5180 (Linking) VI - 24 IP - 1 DP - 2018 Dec TI - Kruppel-like factor 4 mediates cellular migration and invasion by altering RhoA activity. PG - 1-10 LID - 10.1080/15419061.2018.1444034 [doi] AB - Kru ppel like factor 4 (KLF4) is a transcription factor that regulates genes related to differentiation and proliferation. KLF4 also plays a role in metastasis via epithelial to mesenchymal transition. Here, we investigate the function of Klf4 in migration and invasion using mouse embryonic fibroblasts and the RKO human colon cancer cell line. Compared to wild-type, cells lacking Klf4 exhibited increased migration-associated phenotypes. In addition, overexpression of Klf4 in Klf4(-/-) MEFs attenuated the presence of stress fibers to wild-type levels. An invasion assay suggested that lack of Klf4 resulted in increased invasive capacity. Finally, analysis of RhoA showed elevated RhoA activity in both RKO and MEF cells. Taken together, our results strongly support the novel role of KLF4 in a post-translational regulatory mechanism where KLF4 indirectly modulates the actin cytoskeleton morphology via activity of RhoA in order to inhibit cellular migration and invasion. FAU - Brauer, Philip R AU - Brauer PR AD - a Department of Biology , Colgate University , Hamilton , NY , USA. FAU - Kim, Jee Hun AU - Kim JH AD - a Department of Biology , Colgate University , Hamilton , NY , USA. FAU - Ochoa, Humberto J AU - Ochoa HJ AD - a Department of Biology , Colgate University , Hamilton , NY , USA. AD - b Center for Cancer Research, Lab of Cancer Biology and Genetics , National Cancer Institute , Bethesda , MD , USA. FAU - Stratton, Elizabeth R AU - Stratton ER AD - a Department of Biology , Colgate University , Hamilton , NY , USA. FAU - Black, Kathryn M AU - Black KM AD - a Department of Biology , Colgate University , Hamilton , NY , USA. AD - c School of Medicine , Tulane University , New Orleans , LA , USA. FAU - Rosencrans, William AU - Rosencrans W AD - a Department of Biology , Colgate University , Hamilton , NY , USA. FAU - Stacey, Eliza AU - Stacey E AD - a Department of Biology , Colgate University , Hamilton , NY , USA. FAU - Hagos, Engda G AU - Hagos EG AD - a Department of Biology , Colgate University , Hamilton , NY , USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cell Commun Adhes JT - Cell communication & adhesion JID - 101096596 RN - 0 (KLF4 protein, human) RN - 0 (Klf4 protein, mouse) RN - 0 (Kruppel-Like Factor 4) RN - 0 (Kruppel-Like Transcription Factors) RN - 86-01-1 (Guanosine Triphosphate) RN - EC 3.6.5.2 (Rhoc protein, mouse) RN - EC 3.6.5.2 (rhoA GTP-Binding Protein) RN - EC 3.6.5.2 (rhoC GTP-Binding Protein) SB - IM MH - Animals MH - *Cell Movement MH - Cell Shape MH - Embryo, Mammalian/cytology MH - Fibroblasts/*cytology/*metabolism MH - Guanosine Triphosphate/metabolism MH - Kruppel-Like Factor 4 MH - Kruppel-Like Transcription Factors/deficiency/*metabolism MH - Mice, Inbred C57BL MH - Stress Fibers/metabolism MH - Up-Regulation/genetics MH - rhoA GTP-Binding Protein/genetics/*metabolism MH - rhoC GTP-Binding Protein/genetics/metabolism OTO - NOTNLM OT - G protein OT - Kruppel-like factor 4 OT - RhoA OT - actin cytoskeleton OT - invasion OT - migration EDAT- 2018/03/03 06:00 MHDA- 2018/12/18 06:00 CRDT- 2018/03/03 06:00 PHST- 2018/03/03 06:00 [entrez] PHST- 2018/03/03 06:00 [pubmed] PHST- 2018/12/18 06:00 [medline] AID - 10.1080/15419061.2018.1444034 [doi] PST - ppublish SO - Cell Commun Adhes. 2018 Dec;24(1):1-10. doi: 10.1080/15419061.2018.1444034.