Connective tissue growth factor activates pluripotency genes and mesenchymal-epithelial transition in head and neck cancer cells

Cheng Chi Chang, Wen Hao Hsu, Chen Chien Wang, Chun Hung Chou, Mark Yen Ping Kuo, Been Ren Lin, Szu Ta Chen, Shyh Kuan Tai, Min Liang Kuo, Muh Hwa Yang*

*此作品的通信作者

研究成果: Article同行評審

74 引文 斯高帕斯(Scopus)

摘要

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 avb3 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.

原文English
頁(從 - 到)4147-4157
頁數11
期刊Cancer Research
73
發行號13
DOIs
出版狀態Published - 1 7月 2013

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