期刊
ONCOGENESIS
卷 6, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/oncsis.2017.3
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类别
资金
- Science and Technology Program of Guangdong Province [2014A020212155, 2014A030313008]
- PhD Start- up Fund of Natural Science Foundation of Guangdong Province [2015A030310052]
- Natural Science Foundation of China [81325013, 91529301]
- Medical Scientific Research Foundation of Guangdong Province [B2013127]
- Natural Science Foundation of Guangdong Province [2015A030313044]
Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), contribute to tumorigenesis, resistance to chemoradiotherapy and recurrence in human cancers, suggesting targeting CSCs may represent a potential therapeutic strategy. In the current study, we found family with sequence similarity 83, member A (FAM83A) is significantly overexpressed and associated with poorer overall survival and disease-free survival in pancreatic cancer. Overexpression of FAM83A markedly promoted, whereas inhibition of FAM83A decreased, CSC-like traits and chemoresistance both in vitro and in an in vivo mouse model of pancreatic cancer. Furthermore, overexpression of FAM83A activated the well-characterized CSC-associated pathways transforming growth factor-beta (TGF-beta) signaling and Wnt/beta-catenin signaling. Importantly, the FAM83A locus was amplified in a number of human cancers and silencing FAM83A in associated cancer cell lines inhibited activation of the WNT/beta-catenin and TGF-beta signaling pathways and reduced tumorigenicity. Taken together, these results indicate that FAM83A has a vital oncogenic role to promote pancreatic cancer progression and may represent a potential clinical target.
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