期刊
CANCER RESEARCH
卷 73, 期 13, 页码 4147-4157出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-12-4085
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- Taipei Veterans General Hospital, National Taiwan University Hospital [VN101-02]
- National Science Council [101-2321-B-010-015]
- Excellent Translational Medicine Research Projects of National Taiwan University, College of Medicine
- National Taiwan University Hospital [100-C101-014]
- Ministry of Education, Aim for the Top University Plan
- Department of Health, Center of Excellence for Cancer Research [DOH101-TD-C-111-007, DOH101-TD-PB-111-007]
The epithelial-mesenchymal transition (EMT) is a key mechanism in both embryonic development and cancer metastasis. The EMT introduces stem-like properties to cancer cells. However, during somatic cell reprogramming, mesenchymal-epithelial transition (MET), the reverse process of EMT, is a crucial step toward pluripotency. Connective tissue growth factor (CTGF) is a multifunctional secreted protein that acts as either an oncoprotein or a tumor suppressor among different cancers. Here, we show that in head and neck squamous cell carcinoma (HNSCC), CTGF promotes the MET and reduces invasiveness. Moreover, we found that CTGF enhances the stem-like properties of HNSCC cells and increases the expression of multiple pluripotency genes. Mechanistic studies showed that CTGF induces c-Jun expression through alpha v beta 3 integrin and that c-Jun directly activates the transcription of the pluripotency genes NANOG, SOX2, and POU5F1. Knockdown of CTGF in TW2.6 cells was shown to reduce tumor formation and attenuate E-cadherin expression in xenotransplanted tumors. In HNSCC patient samples, CTGF expression was positively correlated with the levels of CDH1, NANOG, SOX2, and POU5F1. Coexpression of CTGF and the pluripotency genes was found to be associated with a worse prognosis. These findings are valuable in elucidating the interplay between epithelial plasticity and stem-like properties during cancer progression and provide useful information for developing a novel classification system and therapeutic strategies for HNSCC. (C) 2013 AACR.
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