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Serine/threonine kinase 33 (STK33) is a serine/threonine kinase and participates in many apoptotic process. Herein, we found that the extracellular signal-regulated kinase 2 (ERK2) was a substrate of STK33. STK33 phosphorylated ERK2 and increased the activity of ERK2 and promote the tumorigenesis of colorectal cancer HCT15 cells. Clinical simple showed that STK33 was highly expression in colorectal cells and tissues. Ex vivo and in vivo studies demonstrated that STK33 accelerate tumorigenic properties in NCM460 cells and athymic nude rats. In vitro kinase assay results indicated that STK33 can phosphorylate ERK2. Ex vivo studies further showed that STK33 can bind with ERK2 and take part in the regulation of ERKs signaling pathway. In short, our results showed that STK33 is a novel upstream kinase of ERK2. It may provide a better prospect for STK33 based prevention and treatment for colorectal cancer patients.

STK33/ERK2 signal pathway contribute the tumorigenesis of colorectal cancer HCT15 cells