Novel role of STRAP in progression and metastasis of colorectal cancer through Wnt/β-catenin signaling

Oncotarget
Guandou YuanPran K Datta

Abstract

Serine-Threonine Kinase Receptor-Associated Protein (STRAP) interacts with a variety of proteins and influences a wide range of cellular processes. Aberrant activation of Wnt/β-catenin signaling has been implicated in the development of colorectal cancer (CRC). Here, we show the molecular mechanism by which STRAP induces CRC metastasis by promoting β-catenin signaling through its stabilization. We have genetically engineered a series of murine and human CRC and lung cancer cell lines to investigate the effects of STRAP on cell migration and invasion in vitro, and on tumorigenicity and metastasis in vivo. Downregulation of STRAP inhibits invasion, tumorigenicity, and metastasis of CRC cells. Mechanistically, STRAP binds with GSK-3β and reduces the phosphorylation, ubiquitylation, and degradation of β-catenin through preventing its binding to the destruction complex. This leads to an inhibition of Wnt/β-catenin signaling and reduction in the expression of downstream targets, such as Cyclin D1, matrix metalloproteinases 2 and 9, and ß-TrCP. In human CRC specimens, higher STRAP expression correlates significantly with β-catenin expression with increased nuclear levels (R =0.696, p < .0001, n =128). Together, these results suggest t...Continue Reading

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Citations

Jun 22, 2016·Oncotarget·Huili LiJiliang Wang
Dec 21, 2017·Cancers·Trung Vu, Pran K Datta
Oct 3, 2018·Cancer Chemotherapy and Pharmacology·Dumnoensun PruksakornChantragan Srisomsap
May 26, 2018·Journal of Cellular Biochemistry·Rakesh Kumar, Shweta Saran
Feb 21, 2019·Investigative Ophthalmology & Visual Science·Justin Ma, Peter Lwigale
Jan 24, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zhenya GuoGuandou Yuan
Feb 29, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yonglian ZengSongqing He
Aug 22, 2021·Signal Transduction and Targeted Therapy·Mei FengDi Zhu

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Methods Mentioned

BETA
xenograft
transfection
immunoprecipitation
PCR
ubiquitination

Software Mentioned

SPSS

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