Epithelial Splicing Regulatory Protein 1 (ESRP1) and 2 (ESRP2) Suppress Cancer Cell Motility via Different Mechanisms [Signal Transduction]

August 20th, 2014 by Ishii, H., Saitoh, M., Sakamoto, K., Kondo, T., Katoh, R., Tanaka, S., Motizuki, M., Masuyama, K., Miyazawa, K.

Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events associated with epithelial phenotypes of cells, and both are down-regulated during the epithelial-mesenchymal transition (EMT). However, little is known about their expression and functions during carcinogenesis. In this study, we found that expression of both ESRP1 and 2 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 2 are re-expressed in the lymph nodes where carcinoma cells metastasize and colonize. In head and neck carcinoma cell lines, ESRP1 and 2 suppressed cancer cell motility through distinct mechanisms: knockdown of ESRP1 affected dynamics of the actin cytoskeleton through induction of Rac1b, whereas knockdown of ESRP2 attenuated cell-cell adhesion through increased expression of EMT-associated transcription factors. Down-regulation of ESRP1 and 2 is thus closely associated with a motile phenotype of cancer cells.