Oncotarget

Research Papers:

C-kit induces epithelial–mesenchymal transition and contributes to salivary adenoid cystic cancer progression

Ya-ling Tang, Yun-long Fan, Jian Jiang, Kai-de Li, Min Zheng, Wei Chen, Xiang-rui Ma, Ning Geng, Qian-ming Chen, Yu Chen and Xinhua Liang _

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Oncotarget. 2014; 5:1491-1501. https://doi.org/10.18632/oncotarget.1606

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Abstract

Ya-ling Tang1,2,*, Yun-long Fan1,*, Jian Jiang1,*, Kai-de Li1, Min Zheng1, Wei Chen1, Xiang-rui Ma1, Ning Geng2, Qian-ming Chen1, Yu Chen2, Xin-hua Liang1,3

1 State Key Laboratory of Oral Diseases West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan, People’s Republic of China

2 Department of Oral Pathology, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan, People’s Republic of China

3 Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology (Sichuan University), Chengdu Sichuan, People’s Republic of China

* These authors contributed equally to this work

Correspondence:

Xinhua Liang, email:

Yu Chen, email:

Keywords:salivary adenoid cystic cancer; epithelial–mesenchymal transition (EMT); c-kit; cancer stem cell; metastasis

Received: November 18, 2013 Accepted: January 6, 2014 Published: January 6, 2014

Abstract

Epithelial–mesenchymal transition (EMT) is associated with salivary adenoid cystic cancer (ACC) progression and metastasis. Here, we report that ectopic overexpression of c-kit in ACC cell lines is sufficient for acquisition of mesenchymal traits, enhanced cell invasion, along with stem cell properties defined by the presence of a CD133+/CD44+ cell subpopulation. c-kit positively regulated expression of known EMT inducers, also activating TGF-β to contribute to EMT. c-kit itself was induced by TGF-β in ACC cell lines and required for TGF-β–induced EMT. Xenograft experiments showed that c-kit cooperated with oncogenic Ras to promote tumorigenesis in vivo. Finally, in human specimens of ACC, we found that c-kit was abnormally overexpressed and correlated with the prognosis of ACC. Our findings define an important function for c-kit in ACC progression by orchestrating EMT, and they implicate this gene product as a marker of poor prognosis in this disease.


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