TY - JOUR
T1 - STK33 promotes growth and progression of pancreatic cancer as a critical downstream mediator of HIF1a
AU - Kong, Fanyang
AU - Kong, Xiangyu
AU - Du, Yiqi
AU - Chen, Ying
AU - Deng, Xuan
AU - Zhu, Jianwei
AU - Du, Jiawei
AU - Li, Lei
AU - Jia, Zhiliang
AU - Xie, Dacheng
AU - Li, Zhaoshen
AU - Xie, Keping
N1 - Funding Information:
This work was supported by grants R01CA172233, R01CA195651, and R01CA198090 from the National Cancer Institute, NIH (to K. Xie) and grant NSFC no. 81402017 and Shanghai Yang Fan Project # 14YF1405600 (to X. Kong) and grant NSFC no. 81402425 (to L. Li) from the National Natural Science Foundation of China.
Publisher Copyright:
© 2017 American Association for Cancer Research.
PY - 2017/12/15
Y1 - 2017/12/15
N2 - 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 HIF1a. 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 HIF1a regulated STK33 via direct binding to a hypoxia response element in its promoter. In showing that dysregulated HIF1a/STK33 signaling promotes PDAC growth and progression, our results suggest STK33 as a candidate therapeutic target to improve PDAC treatment.
AB - 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 HIF1a. 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 HIF1a regulated STK33 via direct binding to a hypoxia response element in its promoter. In showing that dysregulated HIF1a/STK33 signaling promotes PDAC growth and progression, our results suggest STK33 as a candidate therapeutic target to improve PDAC treatment.
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U2 - 10.1158/0008-5472.CAN-17-0067
DO - 10.1158/0008-5472.CAN-17-0067
M3 - Article
C2 - 29038348
AN - SCOPUS:85038441286
SN - 0008-5472
VL - 77
SP - 6851
EP - 6862
JO - Cancer Research
JF - Cancer Research
IS - 24
ER -