FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

Chu, Tian-Li; Zhao, Hongmeng; Li, Yue; Chen, Anran; Sun, Xuan; Ge, Jie

doi:10.1016/j.bbrc.2014.03.019

Cited by 37 publications

(29 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In melanoma cells, ectopic induction of FOXD3 resulted in G1/S phase arrest and suppressed tumor migration and invasion [19]. Also, FOXD3 deficiency promoted breast cancer EMT and lymph node metastases [20]. Our study demonstrated that FOXD3 knockdown increased human anaplastic thyroid cancer cell proliferation and enhanced invasivess and EMT attributes and reduced cancer cell apoptosis.…”

Section: Discussionmentioning

confidence: 75%

FOXD3 regulates anaplastic thyroid cancer progression

et al. 2017

View full text Add to dashboard Cite

Anaplastic thyroid cancer (ATC) is an aggressive malignancy with poor prognosis. It was reported that Forkhead box D3 (FOXD3) transcription factor is associated with several cancers. We investigated its antitumorigenic role of ATC in this study. The ATC cell lines SW1736 and K18 exhibited lower FOXD3 expression than the Nthy-ori-3-1 normal thyroid cell line. FOXD3 downregulation in ATC cell lines promoted invasiveness and epithelial-to-mesenchymal transition (EMT) and decreased cellular apoptosis. FOXD3 silencing also enhanced p-ERK levels in the ATC cell lines, suggesting it negatively regulated MAPK/ERK signaling. Silencing FOXD3 in SW1736 cells also led to generation of larger xenograft tumors with high p-ERK and low E-cadherin levels. Moreover, human ATC samples showed lower FOXD3 and higher p-ERK levels than samples of normal thyroid tissue. These findings demonstrate that FOXD3 acts as a tumor suppressor during anaplastic thyroid carcinogenesis and highlight its potential for clinical application.

show abstract

Section: Discussionmentioning

confidence: 75%

FOXD3 regulates anaplastic thyroid cancer progression

et al. 2017

View full text Add to dashboard Cite

show abstract

“…In cancer cells, FOXD3 has primarily been described as a negative regulator of proliferation and metastasis (30, 31, 34, 35, 44), including hCCCs (43). FOXD3 expression is downregulated in several types of cancers, compared with its levels in corresponding normal tissues (30, 31, 34, 35, 44), as confirmed in hCRCs in here (Figs. 1 and 2).…”

Section: Discussionmentioning

confidence: 99%

“…Loss of FOXD3 expression has been reported as a prognostic marker for patients with neuroblastomas/gliomas and breast/lung/gastric cancers (30, 31, 34, 44). We previously reported that CRC patients overexpressing DCLK1-S had worse overall survival and disease-free interval, compared with patients expressing low levels of DCLK1-S (12).…”

Section: Introductionmentioning

confidence: 99%

FOXD3 Regulates CSC Marker, DCLK1-S, and Invasive Potential: Prognostic Implications in Colon Cancer

Sarkar

O’Connell

Okugawa

et al. 2017

Molecular Cancer Research

View full text Add to dashboard Cite

The 5′ (α)-promoter of the human doublecortin-like kinase 1 (DCLK1) gene becomes epigenetically silenced during colon carcinogenesis, resulting in loss of expression of the canonical long(L)-isoform1 (DCLK1-L) in human colon adenocarcinomas (hCRCs). Instead, hCRCs express a short(S)-isoform2 (DCLK1-S) from an alternate (β)-promoter of DCLK1. The current study, examined if the transcriptional activity of the (β)-promoter is suppressed in normal versus cancerous cells. On the basis of in silico and molecular approaches, it was discovered that FOXD3 potently inhibits the transcriptional activity of the (β)-promoter. FOXD3 becomes methylated in human colon cancer cells (hCCC), with loss of FOXD3 expression, allowing expression of the DCLK1(S) variant in hCCCs/hCRCs. Relative levels of FOXD3/DCLK1(S/L) were measured in a cohort of CRC patient specimens (n = 92), in relation to overall survival (OS). Patients expressing high DCLK1(S), with or without low FOXD3, had significantly worse OS compared with patients expressing low DCLK1(S). The relative levels of DCLK1-L did not correlate with OS. In a pilot retrospective study, colon adenomas from high-risk patients (who developed CRCs in <15 years) demonstrated significantly higher staining for DCLK1(S) + significantly lower staining for FOXD3, compared with adenomas from low-risk patients (who remained free of CRCs). Latter results strongly suggest a prognostic value of measuring DCLK1(S)/FOXD3 in adenomas. Overexpression of DCLK1(S), but not DCLK1(L), caused a significant increase in the invasive potential of hCCCs, which may explain worse outcomes for patients with high DCLK1-S–expressing tumors. On the basis of these data, FOXD3 is a potent repressor of DCLK1-S expression in normal cells; loss of FOXD3 in hCCCs/hCRCs allows upregulation of DCLK1-S, imparting a potent invasive potential to the cells.

show abstract

“…The previous studies demonstrated that FOXD3 overexpression significantly inhibits cell growth in lung cancer cells and induces a potent G0/G1 arrest in melanoma cells [16], which is consistent with our results. In addition, FOXD3 deficiency was demonstrated to promote breast cancer progression by induction of epithelial-mesenchymal transition [17]. In contrast, FOXD3 overexpression inhibits the migration, invasion, and spheroid outgrowth of mutant B-RAF melanoma cells [18].…”

Section: Discussionmentioning

confidence: 99%

FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway

Guo

Yang

et al. 2016

Oncotarget

View full text Add to dashboard Cite

Forkhead box D3 (FOXD3), as a transcriptional repressor, is well known to be involved in the regulation of development. Although FoxD3 is associated with several cancers, its role in colon cancer and the underlying mechanism are still unclear. Here, we first showed that FOXD3 knockdown dramatically increased the proliferation of human colon cancer cells, enhanced cell invasive ability and inhibited cell apoptosis. In vivo xenograft studies confirmed that the FOXD3-knockdown cells were more tumorigenic than the controls. Silencing FOXD3 markedly activated EGFR/Ras/Raf/MEK/ERK pathway in human colon cancer cells. In addition, blocking EGFR effectively decreased the activity of MAPK induced by FOXD3 knockdown. In human cancer tissue, the expression of FOXD3 was reduced, however, the EGFR/Ras/Raf/MEK/ERK pathway was activated. Our study indicates that FOXD3 may play a protective role in human colon formation by regulating EGFR/Ras/Raf/MEK/ERK signal pathway. It is proposed that FOXD3 may have potential as a new therapeutic target in human colon cancer treatment.

show abstract

FoxD3 deficiency promotes breast cancer progression by induction of epithelial–mesenchymal transition

Cited by 37 publications

References 17 publications

FOXD3 regulates anaplastic thyroid cancer progression

FOXD3 regulates anaplastic thyroid cancer progression

FOXD3 Regulates CSC Marker, DCLK1-S, and Invasive Potential: Prognostic Implications in Colon Cancer

FOXD3 is a tumor suppressor of colon cancer by inhibiting EGFR-Ras-Raf-MEK-ERK signal pathway

Contact Info

Product

Resources

About