Research Papers:
EB1 phosphorylation mediates the functions of ASK1 in pancreatic cancer development
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Abstract
Siqi Gao1,*, Youguang Luo1,*, Xiaofan Wu1, Yuanyuan Li1, Yunqiang Zhou1, Rui Lyu1, Min Liu2, Dengwen Li1 and Jun Zhou1,2
1State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of the Ministry of Education, College of Life Sciences, Nankai University, Tianjin 300071, China
2Shandong Provincial Key Laboratory of Animal Resistance Biology, Institute of Biomedical Sciences, College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China
*These authors have contributed equally to this work
Correspondence to:
Jun Zhou, email: [email protected]
Dengwen Li, email: [email protected]
Keywords: EB1; phosphorylation; ASK1; pancreatic cancer
Received: July 05, 2017 Accepted: August 27, 2017 Published: September 18, 2017
ABSTRACT
Pancreatic cancer has a poor prognosis due to its rapid rate of metastasis and frequent late-stage diagnosis. An improved understanding of the molecular mechanisms underlying this disease is urgently needed to promote the development of improved diagnostic tools and more effective therapies. Apoptosis signal-regulating kinase 1 (ASK1) has been shown to be overexpressed in pancreatic cancer and to promote the proliferation of pancreatic cancer cells in a kinase activity-dependent manner. However, the molecular mechanisms by which ASK1 promotes cell proliferation remain to be elucidated. In this study, we report that the phosphorylation of end-binding protein 1 (EB1) at threonine 206 (pT206-EB1), which is catalyzed by ASK1, is increased in pancreatic cancer tissues. We further find that the level of pT206-EB1 correlates with that of ASK1 in cancer tissues. Additionally, ASK1 localizes to spindle poles, and knockdown of ASK1 results in the formation of multipolar spindles. Moreover, we show that depletion of ASK1 or disruption of EB1 phosphorylation inhibits spindle microtubule dynamics in pancreatic cancer cells. Collectively, these findings suggest that EB1 phosphorylation mediates the functions of ASK1 in pancreatic cancer development.
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