Oncode Institute, University Medical Center Utrecht, Utrecht University, the Netherlands.
Center for Molecular Medicine, Molecular Cancer Research, University Medical Center Utrecht, Utrecht University, the Netherlands.
Cancer Res. 2018 May 1;78(9):2356-2369. doi: 10.1158/0008-5472.CAN-17-2511. Epub 2018 Feb 12.
FOXO transcription factors are regulators of cellular homeostasis and putative tumor suppressors, yet the role of FOXO in cancer progression remains to be determined. The data on FOXO function, particularly for epithelial cancers, are fragmentary and come from studies that focused on isolated aspects of cancer. To clarify the role of FOXO in epithelial cancer progression, we characterized the effects of inducible FOXO activation and loss in a mouse model of metastatic invasive lobular carcinoma. Strikingly, either activation or loss of FOXO function suppressed tumor growth and metastasis. We show that the multitude of cellular processes critically affected by FOXO function include proliferation, survival, redox homeostasis, and PI3K signaling, all of which must be carefully balanced for tumor cells to thrive. FOXO proteins are not solely tumor suppressors, but also support tumor growth and metastasis by regulating a multitude of cellular processes essential for tumorigenesis. .
叉头框转录因子（FOXO transcription factors）是细胞内稳态的调节剂和潜在的肿瘤抑制因子，但 FOXO 在癌症进展中的作用仍有待确定。关于 FOXO 功能的数据，特别是针对上皮性癌症的数据，是零散的，并且来自于专注于癌症孤立方面的研究。为了阐明 FOXO 在上皮性癌症进展中的作用，我们在转移性浸润性小叶癌的小鼠模型中对诱导型 FOXO 激活和缺失的作用进行了特征描述。引人注目的是，FOXO 功能的激活或缺失均抑制了肿瘤生长和转移。我们表明，受 FOXO 功能严重影响的多种细胞过程包括增殖、存活、氧化还原内稳态和 PI3K 信号传导，所有这些过程对于肿瘤细胞的生长都必须进行仔细的平衡。FOXO 蛋白不仅是肿瘤抑制因子，而且还通过调节肿瘤发生所必需的多种细胞过程来支持肿瘤生长和转移。
