title: The enforced expression of c-Myc in pig fibroblasts triggers mesenchymal-epithelial transition (MET) via F-actin reorganization and RhoA/Rock pathway inactivation.
abstract: In previous studies from other labs it has been well demonstrated that the ectopic expression of c-Myc in mammary epithelial cells can induce epithelial-mesenchymal transition (EMT), whereas in our pilot experiment, epithelial-like morphological changes were unexpectedly observed in c-Myc-expressing pig fibroblasts [i.e., porcine embryonic fibroblasts (PEFs) and porcine dermal fibroblasts (PDFs)] and pig mesenchymal stem cells, suggesting that the same c-Myc gene is entitled to trigger EMT in epithelial cells and mesenchymal-epithelial transition (MET) in fibroblasts. This prompted us to characterize the existence of a MET in c-Myc-expressing PEFs and PDFs at the molecular level. qRT-PCR, immunofluorescence and western blot analysis illustrated that epithelial-like morphological changes were accompanied by the increased expression of epithelial markers [such as cell adhesion proteins (E-cadherin, α-catenin and Bves), tight junction protein occludin and cytokeratins (Krt8 and Krt18)], the reduced expression of mesenchymal markers [vimentin, fibronectin 1 (FN1), snail1, collagen family of proteins (COL1A1, COL5A2) and matrix metalloproteinase (MMP) family (MMP12 and MMP14)] and the decreased cell motility and increased cell adhesion in c-Myc-expressing PEFs and PDFs. Furthermore, the ectopic expression of c-Myc in pig fibroblasts disrupted the stress fiber network, suppressed the formation of filopodia and lamellipodia, and resulted in RhoA/Rock pathway inactivation, which finally participates in epithelial-like morphological conversion. Taken together, these findings demonstrate, for the first time, that the enforced expression of c-Myc in fibroblasts can trigger MET, to which cytoskeleton depolymerization and RhoA/Rock pathway inactivation contribute.
authors: Cancer Research Institute, Southern Medical University, Guangzhou, China.
authors: Jun-Wen
authors: JW
authors: Shi
authors: Wei
authors: W
authors: Liu
authors: Ting-Ting
authors: TT
authors: Zhang
authors: Sheng-Chun
authors: SC
authors: Wang
authors: Xiao-Lin
authors: XL
authors: Lin
authors: Jing
authors: J
authors: Li
authors: Jun-Shuang
authors: JS
authors: Jia
authors: Hong-Fen
authors: HF
authors: Sheng
authors: Zhi-Fang
authors: ZF
authors: Yao
authors: Wen-Tao
authors: WT
authors: Zhao
authors: Zun-Lan
authors: ZL
authors: Zhao
authors: Rao-Ying
authors: RY
authors: Xie
authors: Sheng
authors: S
authors: Yang
authors: Fei
authors: F
authors: Gao
authors: Quan-Rong
authors: QR
authors: Fan
authors: Meng-Ya
authors: MY
authors: Zhang
authors: Min
authors: M
authors: Yue
authors: Jin
authors: J
authors: Yuan
authors: Wei-Wang
authors: WW
authors: Gu
authors: Kai-Tai
authors: KT
authors: Yao
authors: Dong
authors: D
authors: Xiao
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D020405:Dermis / Q000166:cytology; D058750:Epithelial-Mesenchymal Transition; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D014162:Transfection; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein
keywords: RhoA/Rock pathway; Tibetan miniature pigs; c-Myc; cytoskeleton reorganization; dermal fibroblasts; embryonic fibroblasts; mesenchymal stem cells; mesenchymal-epithelial transition (MET)