FoXA2 promotes esophageal squamous cell carcinoma progression by ZEB2 activation

Abstract

Background It has been reported that Forkhead transcription family member (FOXA2) regulates esophageal squamous cell carcinoma (ESCC) progression. However, the specific mechanism, by which FOXA2 promotes ESCC malignant progression, remains unclear. Materials and methods QRT-PCR and western blotting were applied to measure FOXA2 expression in ESCC tissues, while CCK-8 assay and Transwell assays were used to investigate the effect of FOXA2 on ESCC. Luciferase reporter assay, followed by fast chromatin immunoprecipitation (ChIP) assay, was used to study the relationship between FOXA2 and ZEB2. Results FOXA2 was significantly increased in ESCC tissues, when compared to normal tissues. Moreover, high expression of FOXA2 was also found in ESCC cells. Knockdown of FOXA2 inhibited ESCC cell proliferation, invasion, and migration. Mechanically, FOXA2 was verified to regulate ZEB2 expression at transcription level. Moreover, ZEB2 reversed the inhibitory effect of FOXA2 on ESCC proliferation, invasion, and migration. The relationship between ZEB2 and FOXA2 in ESCC tissues was negative. Conclusions These results indicate that FOXA2 plays a critical role in ESCC progression and may become a potential candidate target for ESCC treatment.

Epigenetically inhibiting CYP3A5 modulates the migration and invasion of esophageal squamous cell carcinoma via ZEB2

“…4A). In addition, consistent with previous studies [30,31], ZEB2 inhibition decreased the invasion and migration capacity of ESCC cells (Supplementary Fig. 4B).…”

FoxA2 is a reliable marker for the diagnosis of yolk sac tumour postpubertal‐type

“…Given the reported FoxA2 positivity in specific tumours, we suggest that FoxA2 should be always adopted in combination with SALL4 in a scenario of metastatic disease diagnosis. [1][2][3][4][5][6][7][8][9][10] Finally, FoxA2 is a nuclear stain that demonstrated no background reactivity, unlike GPC3 (focal background reactivity in necrotic areas) and AFP (diffuse background reactivity in haemorrhagic and/or necrotic areas and cystic-glandular fluid secretion). Therefore, FoxA2 may be easier to interpret than AFP and GPC3 in clinical practice.…”

“…[1][2][3][4][5] In recent years, FoxA2 proved to be crucially involved in several metabolic processes (bile acids and lipids homeostasis, clearance of fatty acids, response to insulin and many others), and its expression has been demonstrated in many tumour types (neuroendocrine lung and prostate tumours, colorectal carcinoma, breast carcinoma, melanoma and many others). [1][2][3][4][5][6][7][8][9][10][11][12] Nettersheim et al found that FoxA2 plays a key role in the progression from seminoma (S) to non-seminomatous germ cell tumours of the testis (NSGCTT), the so-called 'reprogramming' of S cells. [13][14][15][16] Specifically, FoxA2 regulates the expression of genes associated with yolk sac tumour (YST) differentiation [SRY-box 17 (SOX17), glypican-3 (GPC3), afetoprotein (AFP) and others] and is a putative effector of the YST phenotype.…”

Construction and validation of a prognostic model based on stage-associated signature genes of head and neck squamous cell carcinoma: a bioinformatics study

“…FOXA2 binds to the obtained enhancer to activate liver-specific gene transcription to drive colorectal cancer liver metastasis ( 28 ). In addition, FOXA2 activates ZEB2 to promote the invasion and development of esophageal cancer cells ( 29 ). The ZCCHC12 gene is involved in lymph node metastasis and participates in the development of thyroid cancer ( 30 ).…”