Abstract

The mechanisms underlying luteolin-induced inhibition of prostate cancer (PCa) stemness have remained elusive. Here, we report that luteolin suppresses PCa stemness through Wnt signaling by upregulation of FZD6 (frizzled class receptor 6). Luteolin inhibits PCa cell proliferation, migration, self-renewal as well as the expression of prostate cancer stem cell markers in vitro. Through iTRAQ-based quantitative proteomics study, we identified 208 differentially expressed proteins in luteolin-treated PC-3 cells. Subsequent mechanistic analysis revealed that luteolin inhibits Wnt signaling by transcriptional upregulation of FZD6, and thereby suppressing the stemness of PCa cells. Furthermore, we identified FZD6 as a tumor suppressor that can abolish PCa stemness. In summary, our findings demonstrate that suppression of Wnt signaling by upregulation of FZD6 is a mechanism underlying luteolin-induced inhibition of PCa stemness. Our work suggests a new therapeutic strategy against human prostate cancer caused by aberrant activation of Wnt signaling.

Details

Title
Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics
Author
Han, Kun 1 ; Lang, Tingyuan 2 ; Zhang, Zhiqi 1 ; Zhang, Yi 2 ; Sun, Yongning 1 ; Shen, Zan 1 ; Beuerman, Roger W 3 ; Zhou, Lei 3 ; Daliu Min 1 

 Department of Medical Oncology, The Affiliated 6th People’s Hospital of Shanghai Jiaotong University, Shanghai, China 
 Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education), College of Laboratory Medicine, Chongqing Medical University, Chongqing, China 
 Singapore Eye Research Institute, The Academia, 20 College Road, Discovery Tower level 6, Singapore, Singapore; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, 1E Kent Ridge Road, NUHS Tower Block Level 7, Singapore, Singapore; Neuroscience and Behavioral Disorders Program, Duke-NUS Graduate Medical School, 8 college Road, Singapore, Singapore 
Pages
1-13
Publication year
2018
Publication date
Jun 2018
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2049881115
Copyright
© 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.