HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs.

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

Oncogene

journal_title

Oncogene

authors

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 GL

doi

10.1038/onc.2011.365

subject

Has Abstract

pub_date

2012-04-05 00:00:00

pages

1757-70

issue

14

eissn

0950-9232

issn

1476-5594

pii

onc2011365

journal_volume

31

pub_type

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