FOXO Transcription Factors Both Suppress and Support Breast Cancer Progression

被引：62

作者：

Hornsveld, Marten ^{[1
,2
,5
]}

Smits, Lydia M. M. ^{[1
,2
]}

Meerlo, Maaike ^{[1
,2
]}

van Amersfoort, Miranda ^{[3
]}

Koerkamp, Marian J. A. Groot ^{[4
]}

van Leenen, Dik ^{[2
]}

Kloet, David E. A. ^{[2
]}

Holstege, Frank C. P. ^{[4
]}

Derksen, PatrickW. B. ^{[3
]}

Burgering, Boudewijn M. T. ^{[1
,2
]}

Dansen, Tobias B. ^{[2
]}

机构：

[1] Univ Utrecht, Univ Med Ctr Utrecht, Oncode Inst, Utrecht, Netherlands

[2] Univ Utrecht, Univ Med Ctr Utrecht, Ctr Mol Med, Mol Canc Res, Utrecht, Netherlands

[3] Univ Utrecht, Univ Med Ctr Utrecht, Dept Pathol, Utrecht, Netherlands

[4] Princess Maxima Ctr Pediat Oncol, Utrecht, Netherlands

[5] Leiden Univ, Med Ctr, Cell & Chem Biol Dept, Leiden, Netherlands

来源：

CANCER RESEARCH | 2018年 / 78卷 / 09期

关键词：

ANOIKIS RESISTANCE; CELL HOMEOSTASIS; TUMOR-GROWTH; E-CADHERIN; INHIBITION; PATHWAY; PI3K; AKT; METASTASIS; ACTIVATION;

D O I：

10.1158/0008-5472.CAN-17-2511

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. Significance: FOXO proteins are not solely tumor suppressors, but also support tumor growth and metastasis by regulating a multitude of cellular processes essential for tumorigenesis. (C) 2018 AACR.

引用

页码：2356 / 2369

页数：14

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