Induction of pluripotent stem cell genes by connective tissue growth factor promotes mesenchymal-epithelial transition
Date Issued
2012
Date
2012
Author(s)
Hsu, Wen-Hao
Abstract
The epithelial-mesenchymal transition (EMT) is a key mechanism for both embryonic development and cancer metastasis. During somatic cells reprogramming, mesenchymal-epithelial transition (MET), a reverse process of EMT, is a crucial step toward pluripotency, and E-cadherin is critical for this process. Connective tissue growth factor (CTGF) is a member of the CCN family, which is capable of multi-functioning as an oncoprotein or a tumor suppressor among different types of cancers. CTGF exhibit diverse cellular functions in areas such as regulation of cell division, chemotaxis, apoptosis, adhesion, motility, and ion transport, and the regulatory cell motility of CTGF is inversely with EMT. Based on this conception, We investigate the role of CTGF induces mesenchymal-epithelial transition (MET) and promotes stem-like properties in head and neck squamous cell carcinoma (HNSCC). We founded that CTGF promotes MET and stem-like properties in HNSCC cells, we further demonstrated that CTGF promotes MET and activates the transcription of pluripotent stem cell genes Oct4, Sox2 and Nanog through two mechanisms: first, CTGF modifies histone codes on the pluripotent genes, including enrichment of H3K4me3, H3K4Ac, H3K9Ac and reduction of H3K27me3. Second, αvβ3enhance the promoter activity of JUN, which results in an increase of total JUN and phosphorylated JUN expression, leading to transactivation of the expression of the pluripotent stem cell genes. In CTGF transfectant, knockdown of pluripotent gene results in partially MET. Xenotransplantation and patient sample analysis confirm that CTGF induces pluripotent genes expression and MET, which promotes the growth of primary tumors but reduces their invasiveness. This finding will be valuable in elucidating the interplay between EMT/MET and stem cell properties during cancer progression and will provide useful information for developing novel classifications and therapeutic strategies against HNSCC.
Subjects
CTGF
pluripotent stem cell genes
MET
SDGs
Type
thesis
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