Journal of Biological Chemistry
Volume 289, Issue 40, 3 October 2014, Pages 27386-27399
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Cell Biology
Epithelial Splicing Regulatory Proteins 1 (ESRP1) and 2 (ESRP2) Suppress Cancer Cell Motility via Different Mechanisms*

https://doi.org/10.1074/jbc.M114.589432Get rights and content
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ESRP1 (epithelial splicing regulatory protein 1) and ESRP2 regulate alternative splicing events associated with epithelial phenotypes of cells, and both are down-regulated during the epithelial-mesenchymal transition. However, little is known about their expression and functions during carcinogenesis. In this study, we found that expression of both ESRP1 and ESRP2 is plastic: during oral squamous cell carcinogenesis, these proteins are up-regulated relative to their levels in normal epithelium but down-regulated in invasive fronts. Importantly, ESRP1 and ESRP2 are re-expressed in the lymph nodes, where carcinoma cells metastasize and colonize. In head and neck carcinoma cell lines, ESRP1 and ESRP2 suppress cancer cell motility through distinct mechanisms: knockdown of ESRP1 affects the dynamics of the actin cytoskeleton through induction of Rac1b, whereas knockdown of ESRP2 attenuates cell-cell adhesion through increased expression of epithelial-mesenchymal transition-associated transcription factors. Down-regulation of ESRP1 and ESRP2 is thus closely associated with a motile phenotype of cancer cells.

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*

This work was supported by the Vehicle Racing Commemorative Foundation; Japan Society for the Promotion of Science (JSPS) KAKENHI Grants 24791764 and 24592592; the research program of the Project for Development of Innovative Research on Cancer Therapeutics (P-Direct) of the Ministry of Education, Culture, Sports, Science and Technology of Japan; and the JSPS Core-to-Core Program Cooperative International Framework in TGF-β Family Signaling.

3

H. Ishii and K. Miyazawa, unpublished data.

2

The abbreviations used are:

    EMT

    epithelial-mesenchymal transition

    HNSCC

    head and neck squamous cell carcinoma

    OSCC

    oral squamous cell carcinoma

    miRNA/miR

    microRNA.