期刊
NUCLEIC ACIDS RESEARCH
卷 41, 期 18, 页码 8665-8679出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkt579
关键词
-
资金
- Associazione Italiana per la Ricerca sul Cancro
- Progetto d'Interesse Invecchiamento (CNR-MIUR)
- Association for International Cancer Research (AICR)
- Worldwide Cancer Research [11-0622] Funding Source: researchfish
Epithelial-to-mesenchymal transition (EMT) is an embryonic program used by cancer cells to acquire invasive capabilities becoming metastatic. delta Ron, a constitutively active isoform of the Ron tyrosine kinase receptor, arises from skipping of Ron exon 11 and provided the first example of an alternative splicing variant causatively linked to the activation of tumor EMT. Splicing of exon 11 is controlled by two adjacent regulatory elements, a silencer and an enhancer of splicing located in exon 12. The alternative splicing factor and oncoprotein SRSF1 directly binds to the enhancer, induces the production of delta Ron and activates EMT leading to cell locomotion. Interestingly, we now find an important role for hnRNP A1 in controlling the activity of the Ron silencer. HnRNP A1 is able to antagonize the binding of SRSF1 and prevent exon skipping. Notably, hnRNP A1, by inhibiting the production of delta Ron, activates the reversal program, namely the mesenchymal-to-epithelial transition, which instead occurs at the final metastasis sites. Also, hnRNP A1 affects Ron splicing by regulating the expression level of hnRNP A2/B1, which similarly to SRSF1 can promote delta Ron production. These results shed light on how splicing regulation contributes to the tumor progression and provide potential targets to develop anticancer therapies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据