Hakai overexpression effectively induces tumour progression and metastasis in vivo

Scientific Reports
Raquel CastosaAngélica Figueroa

Abstract

At early stages of carcinoma progression, epithelial cells undergo a program named epithelial-to-mesenchymal transition characterized by the loss of the major component of the adherens junctions, E-cadherin, which in consequence causes the disruption of cell-cell contacts. Hakai is an E3 ubiquitin-ligase that binds to E-cadherin in a phosphorylated-dependent manner and induces its degradation; thus modulating cell adhesions. Here, we show that Hakai expression is gradually increased in adenoma and in different TNM stages (I-IV) from colon adenocarcinomas compared to human colon healthy tissues. Moreover, we confirm that Hakai overexpression in epithelial cells drives transformation in cells, a mesenchymal and invasive phenotype, accompanied by the downregulation of E-cadherin and the upregulation of N-cadherin, and an increased proliferation and an oncogenic potential. More importantly, for the first time, we have studied the role of Hakai during cancer progression in vivo. We show that Hakai-transformed MDCK cells dramatically induce tumour growth and local invasion in nude mice and tumour cells exhibit a mesenchymal phenotype. Furthermore, we have detected the presence of micrometastasis in the lung mice, further confirming H...Continue Reading

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Citations

Jun 15, 2018·Journal of the Royal Society, Interface·Hoda ZarkoobEdward A Sander
Nov 17, 2020·Frontiers in Cell and Developmental Biology·Marte SneeggenCinzia Progida
Feb 13, 2021·Cell Communication and Signaling : CCS·Lijie DongXiaorong Li
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Feb 23, 2021·Molecular Therapy. Nucleic Acids·Jiali HuangZhaoxia Wang
May 19, 2021·Archives of Toxicology·Javier De Las RivasAngélica Figueroa

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Methods Mentioned

BETA
ubiquitination
xenograft
transfection
xenografts
PCR
transgenic
acetylation
biopsies

Software Mentioned

GraphPad Prism
Image J
ImageJ

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