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

HIF-1-dependent expression of angiopoietin-like 4 and L1CAM mediates vascular metastasis of hypoxic breast cancer cells to the lungs.
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DOI:
10.1038/onc.2011.365
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发表时间:
2012-04-05
期刊:
影响因子:
8
通讯作者:
Semenza, G. L.
Semenza, G. L.
中科院分区:
医学1区
文献类型:
--
作者:
Zhang, H.;Wong, C. C. L.;Wei, H.;Gilkes, D. M.;Korangath, P.;Chaturvedi, P.;Schito, L.;Chen, J.;Krishnamachary, B.;Winnard, P. T., Jr.;Raman, V.;Zhen, L.;Mitzner, W. A.;Sukumar, S.;Semenza, G. L.

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大多数乳腺癌死亡病例是由于血管转移。乳腺癌细胞必须通过内皮细胞(EC)内渗进入原发肿瘤的血管,然后粘附到EC上并在转移部位外渗。在这项研究中,我们证明,通过RNA干扰或地高辛治疗抑制乳腺癌细胞中的缺氧诱导因子活性(HIF)可抑制原发性肿瘤生长,并通过阻断血管生成素样4(ANGPTL4)和L1细胞粘附分子(L1CAM)的表达来抑制乳腺癌细胞向肺部的转移。ANGPTL4是抑制EC-EC相互作用的分泌因子,而L1CAM增加乳腺癌细胞对EC的粘附。干扰HIF、ANGPTL4或L1CAM表达可抑制乳腺癌细胞向肺的血管转移。
Most cases of breast cancer mortality are due to vascular metastasis. Breast cancer 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 activity (HIF) in breast cancer cells by RNA interference or digoxin treatment inhibits primary tumor growth and also inhibits the metastasis of breast cancer 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 breast cancer cells to ECs. Interference with HIF, ANGPTL4, or L1CAM expression inhibits vascular metastasis of breast cancer cells to the lungs.
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