期刊
FEBS LETTERS
卷 587, 期 6, 页码 631-638出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2012.12.028
关键词
Kindlin-2; GLI1; Hedgehog signaling; Feedback loop; Tumor cell viability
资金
- National Natural Science Foundation of China (NSFC) [30830048]
- Ministry of Science and Technology of China [2010CB912203, 2010CB529402]
- Ministry of Education of China [NSFC31170711]
- Beijing Natural Science Foundation [7120002]
- Leading Academic Discipline Project of Beijing Education Bureau
- Center for Biosciences at Karolinska Institutet, Sweden
Kindlin-2 is engaged in tumor progression. However, the mechanism accounting for Kindlin-2 regulation in tumor cells remained largely unknown. Here, we report a regulatory loop between Kindlin-2 and GLI1, an effector of Hedgehog signaling pathway. We show that Kindlin-2 is transcriptionally downregulated via GLI1 occupancy on the Kindlin-2 promoter. Adversely, we found that Kindlin-2 promotes GLI1 expression through a mechanism involving GSK3 beta inactivation and is independent of Smoothened. Functionally, knockdown of Kindlin-2 cooperates with cyclopamine, a Smoothened antagonist, to decrease the viability of prostate cancer cells. Taken together, targeting the Kindlin-2- GLI1 feedback loop may facilitate the killing of prostate cancer cells. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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