TY - JOUR
T1 - FOXO transcription factors both suppress and support breast cancer progression
AU - Hornsveld, Marten
AU - Smits, Lydia M.M.
AU - Meerlo, Maaike
AU - Van Amersfoort, Miranda
AU - Groot Koerkamp, Marian J.A.
AU - van Leenen, Dik
AU - Kloet, David E.A.
AU - Holstege, Frank C.P.
AU - Derksen, Patrick W.B.
AU - Burgering, Boudewijn M.T.
AU - Dansen, Tobias B.
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85047868304
U2 - 10.1158/0008-5472.CAN-17-2511
DO - 10.1158/0008-5472.CAN-17-2511
M3 - Article
C2 - 29440168
AN - SCOPUS:85047868304
SN - 0008-5472
VL - 78
SP - 2356
EP - 2369
JO - Cancer Research
JF - Cancer Research
IS - 9
ER -