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Publication
A requirement for p120-catenin in the metastasis of invasive ductal breast
cancer.
Authors Kurley SJ, Tischler V, Bierie B, Novitskiy SV, Noske A, Varga Z, Zürrer-Härdi U,
Brandt S, Carnahan RH, Cook RS, Muller WJ, Richmond A, Reynolds AB
Submitted By Submitted Externally on 12/3/2021
Status Published
Journal Journal of cell science
Year 2021
Date Published 3/1/2021
Volume : Pages 134 : Not Specified
PubMed Reference 33097605
Abstract We report here the effects of targeted p120-catenin (encoded by CTNND1;
hereafter denoted p120) knockout (KO) in a PyMT mouse model of invasive ductal
(mammary) cancer (IDC). Mosaic p120 ablation had little effect on primary tumor
growth but caused significant pro-metastatic alterations in the tumor
microenvironment, ultimately leading to a marked increase in the number and size
of pulmonary metastases. Surprisingly, although early effects of p120-ablation
included decreased cell-cell adhesion and increased invasiveness, cells lacking
p120 were almost entirely unable to colonized distant metastatic sites in vivo
The relevance of this observation to human IDC was established by analysis of a
large clinical dataset of 1126 IDCs. As reported by others, p120 downregulation
in primary IDC predicted worse overall survival. However, as in the mice,
distant metastases were almost invariably p120 positive, even in matched cases
where the primary tumors were p120 negative. Collectively, our results
demonstrate a strong positive role for p120 (and presumably E-cadherin) during
metastatic colonization of distant sites. On the other hand, downregulation of
p120 in the primary tumor enhanced metastatic dissemination indirectly via
pro-metastatic conditioning of the tumor microenvironment.




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