FOXO3a Promotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases
FOXO3a Promotes Tumor Cell Invasion through the Induction of Matrix Metalloproteinases
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DOI：
10.1128/mcb.00077-09
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发表时间：
2009-09-15
影响因子：
5.3
通讯作者：
Toker, Alex
中科院分区：
文献类型：
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作者：
Storz, Peter;Doeppler, Heike;Toker, Alex
叉头转录因子FOXO3a在促进肿瘤转移过程中的作用尚不明确。在这里，我们发现癌细胞中FOXO3a的缺失导致肿瘤大小减小，特别是由于侵袭性迁移的减弱。在肿瘤进展过程中，肿瘤质量的增加伴随着肿瘤血管生成前的血清剥夺。我们发现，由于血清饥饿，FOXO3a的核保留导致癌细胞侵袭大大增加。对FOXO3a促进侵袭性迁移机制的探索发现，FOXO3a可诱导基质金属蛋白酶9 （MMP-9）和MMP-13的表达，这两种蛋白均与许多人类实体肿瘤的侵袭和进展有因果关系。我们的研究结果将Forkhead转录因子与以前未被探索的癌症进展功能联系起来，通过促进细胞外基质降解，允许肿瘤侵入邻近组织并最终转移到远处器官。
The role of the Forkhead transcription factor FOXO3a in processes that promote tumor metastasis is poorly defined. Here, we show that depletion of FOXO3a from cancer cells leads to decreased tumor size specifically due to attenuated invasive migration. During tumor progression, an increase in tumor mass is concomitant with serum deprivation prior to tumor angiogenesis. We show that nuclear retention of FOXO3a due to serum starvation results in greatly increased cancer cell invasion. Exploration of the mechanism by which FOXO3a promotes invasive migration revealed that it induces the expression of matrix metalloproteinase 9 (MMP-9) and MMP-13, both of which have been causally linked to the invasion and progression of numerous human solid tumors. Our results link Forkhead transcription factors to a previously unexplored function in cancer progression by promoting extracellular matrix degradation, allowing tumors to invade neighboring tissues and ultimately metastasize to distant organs.