STK33 promotes growth and progression of pancreatic cancer as a critical downstream mediator of HIF-1{alpha}

The serine/threonine kinase STK33 has been implicated in cancer cell proliferation. Here we provide evidence of a critical role for STK33 in the pathogenesis and metastatic progression of pancreatic ductal adenocarcinoma (PDAC). STK33 expression in PDAC was regulated by the hypoxia-inducible transcription factor HIF-1α. In human PDAC specimens, STK33 was overexpressed and associated with poor prognosis. Enforced STK33 expression promoted PDAC proliferation, migration, invasion and tumor growth, whereas STK33 depletion exerted opposing effects. Mechanistic investigations showed that HIF-1α regulated STK33 via direct binding to a hypoxia response element in its promoter. In showing that dysregulated HIF-1α/STK33 signaling promotes PDAC growth and progression, our results suggest STK33 as a candidate therapeutic target to improve PDAC treatment.

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