The Homeotic Protein SIX3 Suppresses Carcinogenesis and Metastasis through Recruiting the LSD1/NuRD(MTA3) Complex

Theranostics
Yu ZhengYan Wang

Abstract

The homeodomain transcription factor SIX3 was recently reported to be a negative regulator of the Wnt pathway and has an emerging role in cancer. However, how SIX3 contributes to tumorigenesis and metastasis is poorly understood. We employed affinity purification and mass spectrometry (MS) to identify the proteins physically associated with SIX3. Genome-wide analysis of the SIX3/LSD1/NuRD(MTA3) complex using a chromatin immunoprecipitation-on-chip approach identified a cohort of target genes including WNT1 and FOXC2, which are critically involved in cell proliferation and epithelial-to-mesenchymal transition. Also, we used flow cytometry, growth curve analysis, EdU incorporation assay, colony formation assays, trans-well invasion assays, immunohistochemical staining and in vivo bioluminescence assay to investigate the function of SIX3 in tumorigenesis. We demonstrate that the SIX3/LSD1/NuRD(MTA3) complex inhibits carcinogenesis in breast cancer cells and suppresses metastasis in breast cancer. SIX3 expression is downregulated in various human cancers and high SIX3 is correlated with improved prognosis. Our study revealed an important mechanistic link between the loss of function of SIX3 and tumor progression, identified a molec...Continue Reading

Citations

Dec 7, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Guan-Jun YangChung-Hang Leung
Jun 19, 2020·Experimental Hematology & Oncology·Bing DongKongming Wu
May 23, 2021·Cell Biochemistry and Biophysics·Chengyuan YangYongmei Song
Oct 2, 2021·Frontiers in Cell and Developmental Biology·Wei LiDa Pang

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Datasets Mentioned

BETA
GSE19615

Methods Mentioned

BETA
Pull-Down
in vitro transcription
PCR
Flow
Assay
affinity purification
coimmunoprecipitation
ChIP
electrophoresis
histone acetylation

Software Mentioned

CellQuest
Harmony
Operetta

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