Angiomotin-p130 inhibits β-catenin stability by competing with Axin for binding to tankyrase in breast cancer

Cell Death & Disease
Jiao YangJin Yang

Abstract

Growing evidence indicates that Angiomotin (Amot)-p130 and Amot-p80 have different physiological functions. We hypothesized that Amot-p130 is a tumor suppressor gene in breast cancer, in contrast with the canonical oncogenicity of Amot-p80 or total Amot. To clarify the role of Amot-p130 in breast cancer, we performed real-time quantitative PCR, western blotting, flow cytometry, microarray, immunofluorescence, immunoprecipitation, and tumor sphere-formation assays in vitro, as well as tumorigenesis and limited-dilution analysis in vivo. In this study, we showed that Amot-p130 inhibited the proliferation, migration, and invasion of breast cancer cells. Interestingly, transcriptional profiles indicated that genes differentially expressed in response to Amot-p130 knockdown were mostly related to β-catenin signaling in MCF7 cells. More importantly, most of the downstream partners of β-catenin were associated with stemness. In a further validation, Amot-p130 inhibited the cancer stem cell potential of breast cancer cells both in vitro and in vivo. Mechanistically, Amot-p130 decreased β-catenin stability by competing with Axin for binding to tankyrase, leading to a further inhibition of the WNT pathway. In conclusions, Amot-p130 funct...Continue Reading

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Citations

Jul 14, 2020·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Y QiuJ-L Liu
Jan 6, 2021·International Journal of Molecular Sciences·Marta Teixeira PintoJoana Paredes

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Methods Mentioned

BETA
flow cytometry
PCR
xenograft
xenografts
pull down
confocal microscopy
co-immunoprecipitation assay
acetylation
pull-down
co-immunoprecipitation

Software Mentioned

BRB
GeneChem
Cell Quest Pro
Ingenuity Pathway Analysis
ArrayTools
GraphPad Prism

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