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

作者：Gao Jianchao; Khan Ammad Aslam; Shimokawa Takashi; Zhan Jun; Stromblad Staffan; Fang Weigang; Zhang Hongquan^*

来源：FEBS LETTERS, 2013, 587(6): 631-638.

DOI：10.1016/j.febslet.2012.12.028

• Kindlin-2
• GLI1
• Hedgehog signaling
• Feedback loop
• Tumor cell viability

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.

• 出版日期2013-3-18
• 单位北京大学