FOXO3a nuclear localisation is associated with good prognosis in luminal-like breast cancer

Abstract

In this study, we investigated the clinical relevance and biological associations of FOXO3a protein expression, using tissue microarrays and immunohistochemistry, in a large series of patients with invasive breast cancer.FOXO3a protein expression showed both nuclear and/or cytoplasmic staining patterns. FOXO3a predominant nuclear expression was positively associated with biomarkers of good prognosis including PgR, FOXA1, and p27 expression. There was an inverse association with mitotic counts, MIB1 growth fraction, C-MYC and PIK3CA expression. With respect to patient outcome, FOXO3a nuclear localisation was associated with longer BC specific survival (p<0.001) and longer distant metastasis free interval (p=0.001), independently of the well-established breast cancer prognostic factors.In conclusion, our results demonstrate the biological and prognostic role of FOXO3a protein expression and its subcellular localization in ER-positive/luminal-like BC possibly through its involvement in controlling cell proliferation.3

Foxo3a drives proliferation in anaplastic thyroid carcinoma via transcriptional regulation of cyclin A1: A paradigm shift that impacts current therapeutic strategies

“…S1B). These data are corroborated by IHC data from other laboratories for normal breast and tumor tissues Habashy et al, 2011;Hu et al, 2004). pFoxO3a T32, indicative of inactive FoxO3a, was elevated ,50% above that of adjacent normal thyroid tissue and was cytoplasmic (supplementary material Fig.…”

Prolyl hydroxylation by EglN2 destabilizes FOXO3a by blocking its interaction with the USP9x deubiquitinase

“…Consistent with this, decreased expression of FOXO3a associated with poor outcomes in breast cancer and neuroblastoma (Sunayama et al 2011;Jiang et al 2013;Santo et al 2013). Conversely, FOXO3a nuclear localization is associated with good prognosis in luminal-like breast cancer (Habashy et al 2011). Moreover, exogenous expression of FOXO3a inhibits tumor growth in vitro and in vivo in breast cancer (Hu et al 2004;Yang et al 2008;Lin et al 2011;Sisci et al 2013).…”

Expression and prognosis of FOXO3a and HIF-1α in nasopharyngeal carcinoma

“…Moreover, studies have shown that FOXO3a could serve as an independent predictor for survival in these cancers Fei et al 2009;Habashy et al 2011;Shiota et al 2010;Shi et al 2009). However, with regard to the possible role of FOXO3a on NPC patients' prognosis, it is still unclear thus far.…”

“…However, phosphorylation of FOXO3a by PI3K/Akt enhances its interaction with 14-3-3 protein and promotes FOXO3a nuclear export to cytoplasm, resulting in its ubiquitination and proteasomal degradation, thereby blocking its activity (Brunet et al 1999). Emerging evidences suggest that aberrant expression of FOXO3a is associated with hepatocellular carcinoma ), ovarian cancer (Fei et al 2009), breast cancer (Habashy et al 2011), urothelial cancer (Shiota et al 2010, and thyroid cancer (Karger et al 2008). These results suggest that FOXO3a may play a crucial role in the development and progression of human cancers.…”