Vascular Program, Institute for Cell Engineering, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Trends Mol Med. 2012 Sep;18(9):534-43. doi: 10.1016/j.molmed.2012.08.001. Epub 2012 Aug 23.
Breast cancers contain regions of intratumoral hypoxia in which reduced O(2) availability activates the hypoxia-inducible factors HIF-1 and HIF-2, which increase the transcription of genes encoding proteins that are required for many important steps in cancer progression. Recently, HIFs have been shown to play critical roles in the metastasis of breast cancer to the lungs through the transcriptional activation of genes encoding angiopoietin-like 4 and L1 cell adhesion molecule, which promote the extravasation of circulating cancer cells from the lung vasculature, and the lysyl oxidase family members LOX, LOXL2, and LOXL4, which promote invasion and metastatic niche formation. Digoxin, a drug that inhibits HIF-1 activity, blocks primary tumor growth, vascularization, invasion, and metastasis in ex vivo and in vivo assays.
乳腺癌中存在肿瘤内缺氧区域，其中减少的 O(2) 供应会激活缺氧诱导因子 HIF-1 和 HIF-2，从而增加编码在癌症进展的许多重要步骤中所需的蛋白质的基因的转录。最近，已经表明 HIF 在通过转录激活编码血管生成素样 4 和 L1 细胞粘附分子的基因促进循环癌细胞从肺脉管系统逸出方面，在乳腺癌转移到肺部方面发挥关键作用，并且赖氨酸氧化酶家族成员 LOX、LOXL2 和 LOXL4 促进侵袭和转移生态位形成。地高辛是一种抑制 HIF-1 活性的药物，可阻断体外和体内测定中的原发性肿瘤生长、血管生成、侵袭和转移。
