C-kit induces epithelial-mesenchymal transition and contributes to salivary adenoid cystic cancer progression
| Autor: | Jian Jiang, Ning Geng, Yu Chen, Ya-ling Tang, Xin-hua Liang, Xiang-rui Ma, Min Zheng, Yun-long Fan, Qianming Chen, Kai-de Li, Wei Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Pathology
Fluorescent Antibody Technique Apoptosis medicine.disease_cause Metastasis Immunoenzyme Techniques Cell Movement Transforming Growth Factor beta Tumor Cells Cultured epithelial–mesenchymal transition (EMT) biology Reverse Transcriptase Polymerase Chain Reaction Flow Cytometry Prognosis Salivary Gland Neoplasms Carcinoma Adenoid Cystic Gene Expression Regulation Neoplastic Survival Rate Proto-Oncogene Proteins c-kit Cell Transformation Neoplastic Oncology embryonic structures Disease Progression Neoplastic Stem Cells Stem cell psychological phenomena and processes Research Paper Signal Transduction medicine.medical_specialty cancer stem cell Epithelial-Mesenchymal Transition Blotting Western Real-Time Polymerase Chain Reaction behavioral disciplines and activities Cancer stem cell medicine Carcinoma metastasis Humans Neoplasm Invasiveness Epithelial–mesenchymal transition RNA Messenger salivary adenoid cystic cancer Cell Proliferation CD44 Mesenchymal stem cell medicine.disease stomatognathic diseases Genes ras c-kit biology.protein Cancer research Carcinogenesis |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | // Ya-ling Tang 1,2,* , Yun-long Fan 1,* , Jian Jiang 1,* , Kai-de Li 1 , Min Zheng 1 , Wei Chen 1 , Xiang-rui Ma 1 , Ning Geng 2 , Qian-ming Chen 1 , Yu Chen 2 , Xin-hua Liang 1,3 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. |
| Databáze: | OpenAIRE |
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