Research Papers:

Over-expression of CKS1B activates both MEK/ERK and JAK/STAT3 signaling pathways and promotes myeloma cell drug-resistance

Lei Shi, Siqing Wang, Maurizio Zangari, Hongwei Xu, Thai M. Cao, Chunjiao Xu, Yong Wu, Fang Xiao, Yinghong Liu, Ye Yang, Mohamed Salama, Guiyuan Li, Guido Tricot and Fenghuang Zhan _

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Oncotarget. 2010; 1:22-33. https://doi.org/10.18632/oncotarget.105

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Received: April 28, 2010, Accepted: April 30, 2010, Published: May 15, 2010

Here we demonstrate the crucial role of CKS1B in multiple myeloma (MM) progression and define CKS1B-mediated SKP2/p27Kip1-independent down-stream signaling pathways. Forced-expression of CKS1B in MM cells increased cell multidrug-resistance. CKS1B activates STAT3 and MEK/ERK pathways. In contrast, SKP2 knockdown or p27Kip1 over-expression resulted in activation of the STAT3 and MEK/ERK pathways. Further investigations showed that BCL2 is a downstream target of MEK/ERK signaling. Stimulation of STAT3 and MEK/ERK signaling pathways partially abrogated CKS1B knockdown induced MM cell death and growth inhibition. Targeting STAT3 and MEK/ ERK signaling pathways by specific inhibitors induced significant MM cell death and growth inhibition in CKS1B-overexpressing MM cells and their combinations resulted in synergy. Thus, our findings provide a rationale for targeting STAT3 and MEK/ERK/ BCL2 signaling in aggressive CKS1B-overexpressing MM.


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