Downregulation of FOXO6 in breast cancer promotes epithelial&amp;ndash;mesenchymal transition and facilitates migration and proliferation of cancer cells

Ye, Hui; Duan, Meiling

doi:10.2147/cmar.s157661

Cited by 18 publications

(16 citation statements)

References 35 publications

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“…17,18 In this study, we showed that In our previous study, we reported FOXO6 is downregulated in breast cancer, the function of which is to regulate migration, invasion, and epithelial-mesenchymal transition through transcriptionally regulated Sirt6 expression. 19 As Li, W. 20 reported that FOXN3 was a transcriptional repressor and promoted progression of hormonally responsive breast cancer through inhibition of GATA3. Interestingly, although we revealed that FOXN4 is another tumor driver, the mechanism is distinct.…”

Section: Discussionmentioning

confidence: 99%

<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>

Duan

2020

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Background: Fork head domain-containing gene family (Fox) transcription factors, consisting of over 20 members, are involved in the progression of certain types of tumor. However, whether FOXN4 is involved in carcinogenesis and tumor progression is still unclear. Purpose: In this study, we investigated the clinicopathological significance and the underlying mechanism of FOXN4 in breast cancer. Methods and results: We examined the lower expression of FOXN4 in breast cancer tissues and cancer cell lines. The expression of FOXN4 is negatively correlated with tumor size and lymph node metastasis. Using CCK-8 assay, colony formation assay, wound healing assay, and Transwell assay, we revealed that FOXN4 notably decreased breast cancer cell proliferation, epithelial-mesenchymal transition and invasion in vitro. In addition, quantitative chromatin immunoprecipitation and luciferase assays determined that FOXN4 was able to directly bind with the promoter of P53. RT-qPCR and Western blotting analysis showed that FOXN4 could directly activate P53 expression. Functionally, P53 knockdown rescued the tumor inhibition effects of FOXN4 in breast cancer cells. Conclusion: The present study provides new insights into the role of FOXN4 in breast cancer progression and suggests FOXN4 might represent a potential therapeutic target in breast cancer by modulating P53.

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Section: Discussionmentioning

confidence: 99%

<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>

Duan

2020

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“…The fact that FOXOs are involved in regulating cell migration is further supported by the observation that FOXO6 regulates Plxna4-mediated neuronal migration during development [ 76 ]. However, when overexpressed, FOXO6 has also been shown to inhibit breast cancer cell migration and invasion [ 77 ]. These conflicting findings may reflect the cell type–specific roles of FOXOs in cell migration and metastasis.…”

Section: Tumour-suppressive Roles Of Foxosmentioning

confidence: 99%

FOXO transcription factor family in cancer and metastasis

Jiramongkol

Lam

2020

Cancer Metastasis Rev

183

118

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Forkhead box O (FOXO) transcription factors regulate diverse biological processes, affecting development, metabolism, stem cell maintenance and longevity. They have also been increasingly recognised as tumour suppressors through their ability to regulate genes essential for cell proliferation, cell death, senescence, angiogenesis, cell migration and metastasis. Mechanistically, FOXO proteins serve as key connection points to allow diverse proliferative, nutrient and stress signals to converge and integrate with distinct gene networks to control cell fate, metabolism and cancer development. In consequence, deregulation of FOXO expression and function can promote genetic disorders, metabolic diseases, deregulated ageing and cancer. Metastasis is the process by which cancer cells spread from the primary tumour often via the bloodstream or the lymphatic system and is the major cause of cancer death. The regulation and deregulation of FOXO transcription factors occur predominantly at the post-transcriptional and post-translational levels mediated by regulatory non-coding RNAs, their interactions with other protein partners and co-factors and a combination of post-translational modifications (PTMs), including phosphorylation, acetylation, methylation and ubiquitination. This review discusses the role and regulation of FOXO proteins in tumour initiation and progression, with a particular emphasis on cancer metastasis. An understanding of how signalling networks integrate with the FOXO transcription factors to modulate their developmental, metabolic and tumour-suppressive functions in normal tissues and in cancer will offer a new perspective on tumorigenesis and metastasis, and open up therapeutic opportunities for malignant diseases.

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“…Forkhead transcription factor family (FOXO) are tumour suppressor regulating cell proliferation and promoting apoptosis in BC. Recent in vitro studies have demonstrated that expression of FOXO6 promotes BC migration and invasion by aiding EMT [114]. Elevated FOXO6 in BCs could be, at least in part, due to reduced activity of the PI3K/AKT pathway.…”

Section: Key Lvi-related Biomarkersmentioning

confidence: 99%

Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype

et al. 2020

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Lymphovascular invasion (LVI) is associated with poor outcome in breast cancer (BC); however, its underlying mechanisms remain ill-defined. LVI in BC develops through complex molecular pathways involving not only the interplay with the surrounding microenvironment along with endothelial cells lining the lymphovascular spaces but also changes in the malignant epithelial cells with the acquisition of more invasive and migration abilities. In this review, we focus on the key features that enable tumour cell detachment from the primary niche, their migration and interaction with the surrounding microenvironment as well as the crosstalk with the vascular endothelial cells, which eventually lead to intravasation of tumour cells and LVI. Intravascular tumour cell survival and migration, their distant site extravasation, stromal invasion and growth are part of the metastatic cascade. Cancer cell migration commences with loss of tumour cells' cohesion initiating the invasion and migration processes which are usually accompanied by the accumulation of specific cellular and molecular changes that enable tumour cells to overcome the blockades of the extracellular matrix, spread into surrounding tissues and interact with stromal cells and immune cells. Thereafter, tumour cells migrate further via interacting with lymphovascular endothelial cells to penetrate the vessel wall leading ultimately to intravasation of cancer cells. Exploring the potential factors influencing cell migration in LVI can help in understanding the underlying mechanisms of LVI to identify targeted therapy in BC.

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Downregulation of FOXO6 in breast cancer promotes epithelial–mesenchymal transition and facilitates migration and proliferation of cancer cells

Cited by 18 publications

References 35 publications

<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>

<p>FOXN4 Inhibits Breast Cancer Progression By Direct Activation Of P53</p>

FOXO transcription factor family in cancer and metastasis

Molecular Complexity of Lymphovascular Invasion: The Role of Cell Migration in Breast Cancer as a Prototype

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