Abstract:
:Most cases of breast cancer (BrCa) mortality are due to vascular metastasis. BrCa cells must intravasate through endothelial cells (ECs) to enter a blood vessel in the primary tumor and then adhere to ECs and extravasate at the metastatic site. In this study we demonstrate that inhibition of hypoxia-inducible factor (HIF) activity in BrCa cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of BrCa cells to the lungs by blocking the expression of angiopoietin-like 4 (ANGPTL4) and L1 cell adhesion molecule (L1CAM). ANGPTL4 is a secreted factor that inhibits EC-EC interaction, whereas L1CAM increases the adherence of BrCa cells to ECs. Interference with HIF, ANGPTL4 or L1CAM expression inhibits vascular metastasis of BrCa cells to the lungs.
journal_name
Oncogenejournal_title
Oncogeneauthors
Zhang H,Wong CC,Wei H,Gilkes DM,Korangath P,Chaturvedi P,Schito L,Chen J,Krishnamachary B,Winnard PT Jr,Raman V,Zhen L,Mitzner WA,Sukumar S,Semenza GLdoi
10.1038/onc.2011.365subject
Has Abstractpub_date
2012-04-05 00:00:00pages
1757-70issue
14eissn
0950-9232issn
1476-5594pii
onc2011365journal_volume
31pub_type
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