A feedback regulation between Kindlin-2 and GLI1 in prostate cancer cells.

Abstract

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 GSK3β 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.

• Authors: Jianchao Gao, Ammad Aslam Khan, Takashi Shimokawa, Jun Zhan, Staffan Strömblad, Weigang Fang, Hongquan Zhang
• Journal: FEBS letters (FEBS Lett) Vol. 587 Issue 6 Pg. 631-8 (Mar 18 2013) ISSN: 1873-3468 [Electronic] England
• PMID: 23337877 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Chemical References

• FERMT3 protein, human
• GLI1 protein, human
• Membrane Proteins
• Neoplasm Proteins
• Receptors, G-Protein-Coupled
• SMO protein, human
• Smoothened Receptor
• Transcription Factors
• Veratrum Alkaloids
• Zinc Finger Protein GLI1
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Glycogen Synthase Kinase 3
• cyclopamine

Topics

• Cell Line, Tumor
• Cell Survival (drug effects)
• Feedback, Physiological (drug effects)
• Gene Expression Regulation, Neoplastic (drug effects)
• Gene Knockdown Techniques
• Glycogen Synthase Kinase 3 (genetics, metabolism)
• Glycogen Synthase Kinase 3 beta
• Humans
• Male
• Membrane Proteins (genetics, metabolism)
• Neoplasm Proteins (genetics, metabolism)
• Promoter Regions, Genetic
• Prostatic Neoplasms (genetics, metabolism, pathology)
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Signal Transduction (drug effects)
• Smoothened Receptor
• Transcription Factors (genetics, metabolism)
• Transcription, Genetic (drug effects)
• Veratrum Alkaloids (pharmacology)
• Zinc Finger Protein GLI1