EMT and stemness: flexible processes tuned by alternative splicing in development and cancer progression

Molecular Cancer

Review

Claudio Sette¹  Chiara Naro¹  Claudia Ghigna²  Davide Pradella³ 

[1] Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133, Rome, Italy;Laboratory of Neuroembryology, Fondazione Santa Lucia, 00143, Rome, Italy;Istituto di Genetica Molecolare – Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, 27100, Pavia, Italy;Istituto di Genetica Molecolare – Consiglio Nazionale delle Ricerche, via Abbiategrasso 207, 27100, Pavia, Italy;Dipartimento di Biologia e Biotecnologie, ‘Lazzaro Spallanzani’ - Universita` degli Studi di Pavia, via Ferrata 9, 27100, Pavia, Italy;

关键词: Alternative splicing;    EMT;    Stem cell differentiation;    Cancer stem cells;    Tumor progression;    RNA binding proteins;   

DOI  :  10.1186/s12943-016-0579-2

 received in 2016-10-25, accepted in 2016-12-25,  发布年份 2017

来源: Springer

【 摘 要 】

Epithelial-to-mesenchymal transition (EMT) is associated with metastasis formation as well as with generation and maintenance of cancer stem cells. In this way, EMT contributes to tumor invasion, heterogeneity and chemoresistance. Morphological and functional changes involved in these processes require robust reprogramming of gene expression, which is only partially accomplished at the transcriptional level. Alternative splicing is another essential layer of gene expression regulation that expands the cell proteome. This step in post-transcriptional regulation of gene expression tightly controls cell identity between epithelial and mesenchymal states and during stem cell differentiation. Importantly, dysregulation of splicing factor function and cancer-specific splicing isoform expression frequently occurs in human tumors, suggesting the importance of alternative splicing regulation for cancer biology.In this review, we briefly discuss the role of EMT programs in development, stem cell differentiation and cancer progression. Next, we focus on selected examples of key factors involved in EMT and stem cell differentiation that are regulated post-transcriptionally through alternative splicing mechanisms. Lastly, we describe relevant oncogenic splice-variants that directly orchestrate cancer stem cell biology and tumor EMT, which may be envisioned as novel targets for therapeutic intervention.

【 授权许可】

CC BY   
© The Author(s). 2017