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bioRxiv · 10.1101/2022.05.16.492181

Post-transcriptional control of SRSF9 promotes the epithelial-to-mesenchymal transition (EMT) in colorectal cancer cells

Rao, C.·Svoboda, R. A.·Southekal, S.·Vieira, H. M.·Huisman, D. H.·Chatterjee, D.·Guda, C.·Fisher, K. W.·Anczukow, O.·Lewis, R. E.
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Abstract

In human colorectal cancer (CRC) cells the Raf/MEK/ERK scaffold Kinase Suppressor of Ras 1 (KSR1)-dependent signaling is required for the epithelial-to-mesenchymal transition (EMT)-like phenotype. Here we show that KSR1 promotes the association of differentially spliced mRNA bearing recognition sites for the Serine/Arginine-Rich (SR) splicing factor SRSF9. CRISPR/Cas9 disruption of KSR1 destabilizes SRSF9 protein, which interacts preferentially with mRNA encoding Epithelial Stromal Interaction 1 (EPSTI1). EPSTI1 protein mediates Ras and KSR1-dependent induction of EMT. Analysis of EPSTI1 splice variants reveals that inclusion of exon 8 is critical to the ability of EPSTI1 to promote the E-to N-cadherin switch and CRC cell motile and invasive behavior. These data reveal a mechanism in CRC cells in which Ras-induced and KSR1-dependent signaling affects pre-mRNA splicing to control behaviors critical to cancer cell dissemination and metastasis.

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Rao, C., Svoboda, R. A., Southekal, S., Vieira, H. M., Huisman, D. H., Chatterjee, D., Guda, C., Fisher, K. W., Anczukow, O., Lewis, R. E.. 2022-05-17. Post-transcriptional control of SRSF9 promotes the epithelial-to-mesenchymal transition (EMT) in colorectal cancer cells. https://doi.org/10.1101/2022.05.16.492181

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