期刊
CELL CYCLE
卷 12, 期 7, 页码 1119-1127出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cc.24164
关键词
c-Myc; Tibetan miniature pigs; embryonic fibroblasts; dermal fibroblasts; mesenchymal stem cells; mesenchymal-epithelial transition (MET); cytoskeleton reorganization; RhoA/Rock pathway
类别
资金
- State Key Development Program for Basic Research of China [2010CB529400]
- Joint Funds of the National Natural Science Foundation of China-Guangdong Province [u0732006]
- National Natural Science Foundation of China [81172587]
- Natural Science Foundation of Guangdong Province of China [9151063101000015]
- Science and Technology Planning Project of Guangdong Province of China [2009B060300008]
- Ministry of Science and Technology National Basic Research Program of China (973 program) [2011CBA01006]
- Science and Technology Talented Man Foundation of Outstanding Young and Middle-aged People of Southern Medical University
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, alpha-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.
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