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The effects on oncogenic pathway, signaling, by RSK2 N-terminal kinase inhibitor (BI-D1870) in Mantle cell lymphoma-derived cell lines.

ABSTRACT: The effects on oncogenic pathway, signaling, by RSK2 N-terminal kinase inhibitor (BI-D1870) in Mantle cell lymphoma-derived cell lines.

PROVIDER: PRJNA614962 | ENA |

REPOSITORIES: ENA

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The effects on oncogenic pathway, signaling, by RSK2 N-terminal kinase inhibitor (BI-D1870) in Mantle cell lymphoma-derived cell lines.

Project description:RSK2 is a serine/threonine kinase downstream signaling mediator in the RAS/ERK signaling pathway and may be a therapeutic target in mantle cell lymphoma (MCL). RSK2-Ser227 in the N-terminal kinase domain (NTKD) of RSK2 was found to be ubiquitously active in five MCL-derived cell lines and in tumor tissues derived from five MCL patients. BI-D1870, an inhibitor specific to RSK2-NTKD, caused RSK2-Ser227 dephosphorylation, and thereby, induced dose-dependent growth inhibition via G2/M cell cycle blockade and apoptosis. Comparative gene expression profiling of the MCL-derived cell lines showed that inhibition of RSK2-Ser227 by BI-D1870 caused downregulation of oncogenes, such c-MYC and MYB; anti-apoptosis genes, such as BCL2 and BCL2L1; genes for B cell development, including IKZF1, IKZF3 and PAX5; and genes constituting the B cell receptor signaling pathway, such as CD19, CD79B and BLNK. These findings show that targeting of RSK2-Ser227 enables concomitant blockade of pathways that are critically important in B cell tumorigenesis.

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