Journal
JOURNAL OF CELL SCIENCE
Volume 134, Issue 6, Pages -Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.250639
Keywords
p120 catenin; Breast metastasis; Colonization
Categories
Funding
- Vanderbilt University Core Resources: VUMC Cell Imaging Shared Resource [CA68485, DK20593, DK58404, HD15052, DK59637, EY08126]
- VMC Flow Cytometry Shared Resource [P30 CA68485, DK058404]
- National Institutes of Health (NIH) [R01 CA111947, R01 CA55724, 2PO1CA099031-06A1, BC083306]
- Vanderbilt Cancer Center (NIH) [P30 CA068485]
- Vanderbilt Breast SPORE (NIH) [P50 CA98131]
Ask authors/readers for more resources
The study shows that p120 plays a positive role in the tumor microenvironment and metastatic colonization of distant sites, while its downregulation in primary tumors indirectly enhances metastatic dissemination.
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) duringmetastatic 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available