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Status |
Public on Jul 09, 2019 |
Title |
SFRPs Are Biphasic Modulators of Wnt Signaling-elicited Cancer Stem Cell Properties beyond Extracellular Control |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Secreted frizzled-related proteins (SFRPs) are mainly known for their role as extracellular modulators and tumor suppressors that down-regulate Wnt signaling. Using the established (CRISPR/Cas9 targeting promoters of SFRPs and targeting SFRPs transcript) system, we find that nuclear SFRPs interact with β-catenin and either promote or suppress TCF4 recruitment. SFRPs bind with β-catenin on both their N and C termini, which the repressive effects caused by SFRP-β-catenin-N-terminus binding overpower the promoting effects of their binding at the C terminus. By high Wnt activity, β-catenin and SFRPs only bind with their C termini, which results in the up-regulation of β-catenin transcriptional activity and cancer stem cell (CSC)-related genes. Furthermore, we identify disulfide bonds of the CRD domain and two threonine phosphorylation events of the NTR domain of SFRPs that are essential for their role as biphasic modulators, suggesting that SFRPs are biphasic modulators of Wnt signaling-elicited CSC properties beyond extracellular control.
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Overall design |
Total cellular RNA was extracted from HM20 Mock and SFRP1-5-expressing stable clones after treatment with Wnt3a-containing medium for 24 hours.
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Contributor(s) |
Lee J |
Citation missing |
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Submission date |
Jul 08, 2019 |
Last update date |
Jul 11, 2019 |
Contact name |
Jia-Lin Lee |
E-mail(s) |
jllee@life.nthu.edu.tw
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Organization name |
National Tsing Hua University
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Street address |
101, Sec. 2, Kuang Fu Road
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City |
Hsinchu |
ZIP/Postal code |
30013 |
Country |
Taiwan |
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Platforms (1) |
GPL16951 |
Phalanx Human OneArray Ver. 6 Release 1 |
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Samples (6)
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GSM3930465 |
HM20 SFRP1 cells_Wnt3A treated 24h_rep1 |
GSM3930466 |
HM20 SFRP2 cells_Wnt3A treated 24h_rep1 |
GSM3930467 |
HM20 SFRP3 cells_Wnt3A treated 24h_rep1 |
GSM3930468 |
HM20 SFRP4 cells_Wnt3A treated 24h_rep1 |
GSM3930469 |
HM20 SFRP5 cells_Wnt3A treated 24h_rep1 |
GSM3930470 |
HM20 Mock cells_Wnt3A treated 24h_rep1 |
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Relations |
BioProject |
PRJNA553187 |