FOXQ1 Regulates Epithelial-Mesenchymal Transition in Human Cancers

Abstract

Epithelial-mesenchymal transition (EMT) in cancer cells plays a pivotal role in determining metastatic prowess, but knowledge of EMT regulation remains incomplete. In this study, we defined a critical functional role for the Forkhead transcription factor FOXQ1 in regulating EMT in breast cancer cells. FOXQ1 expression was correlated with high-grade basal-like breast cancers and was associated with poor clinical outcomes. RNAimediated suppression of FOXQ1 expression in highly invasive human breast cancer cells reversed EMT, reduced invasive ability, and alleviated other aggressive cancer phenotypes manifested in 3-dimensional Matrigel (BD Biosciences) culture. Conversely, enforced expression of FOXQ1 in differentiated human mammary epithelial cells (HMLER) or epithelial cancer cell lines provoked an epithelial to mesenchymal morphologic change, gain of stem cell-like properties, and acquisition of resistance to chemotherapy-induced apoptosis. Mechanistic investigations revealed that FOXQ1-induced EMT was associated with transcriptional inactivation of the epithelial regulator E-cadherin (CDH1). Our findings define a key role for FOXQ1 in regulating EMT and aggressiveness in human cancer. Cancer Res; 71(8); 3076-86. Ó2011 AACR.

Contribution of upregulated dipeptidyl peptidase 9 (DPP9) in promoting tumoregenicity, metastasis and the prediction of poor prognosis in non‐small cell lung cancer (NSCLC)

“…In our study, the expression of E‐cadherin and vimentin (epithelial markers) were significantly increased in shDPP9‐transfected cells. Loss of E‐cadherin is considered to be a critical event in EMT38 that regulates cellular dimensions and cell shape 39. The loss of functional E‐cadherin is thus a hallmark of EMT 40, 41.…”

The hepatic FOXQ1 transcription factor regulates glucose metabolism in mice

“…Mice with FOXQ1 deficiency exhibit a lack of gastric acid secretion [19]. Accumulating evidence suggests that increased FOXQ1 expression is correlated with metastasis and poor prognosis for multiple human cancers, including breast cancer, colon cancer and lung cancer [20][21][22][23].…”

FOXQ1 (forkhead box Q1)

“…Prognosis FOXQ1 expression in breast cancer patients is associated with poor survival, high grade, metastatic status and basal-like phenotype (Qiao et al, 2011). Oncogenesis FOXQ1 overexpression was observed in invasive breast cancer cell lines compared to non-invasive.…”

“…FOXQ1 expression increases breast cancer cell proliferation, migration and invasion in vitro and metastasis in vivo (Zhang et al, 2011). FOXQ1 promotes an EMT phenotype through transcriptional regulation of CDH1 (Qiao et al, 2011;Zhang et al, 2011).…”

“…Wnt activity directly correlates with FOXQ1 expression in colorectal cancer cell lines and β-catenin can bind to the promoter of FOXQ1 and increase transcription . FOXQ1 expression can induce an EMT phenotype (Qiao et al, 2011;Abba et al, 2013). FOXQ1 does not increase growth but seems to protect from apoptosis (Kaneda et al, 2010;Qiao et al, 2011;Abba et al, 2013).…”