BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial–mesenchymal transition and angiogenesis

Zhao, Yan; Gao, Jiajia; Xie, Xiufeng; Peng, Nan; Liu, Fang; Sun, Yulin; Zhao, Xiaohang

doi:10.1002/cam4.3884

Cited by 20 publications

(22 citation statements)

References 46 publications

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“…Zhao et al have identified BTB Domain and CNC Homolog 1 ( BACH1 ) TF as promoter of EMT in esophageal squamous cell carcinoma cells. They have shown that BACH1 directly binds to the promoter region of CDH2, SNAI2, Vimentin, and VEGFC genes and regulate their transcription [ 228 ]. BACH1 was further shown to induce EMT and promote pancreatic cancer metastasis (Sato et al, Cancer Res.…”

Section: Other Emt Tfsmentioning

confidence: 99%

Epithelial–mesenchymal transition and its transcription factors

et al. 2021

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Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors including the master regulators of EMT, with the ability to regulate the EMT process directly. In this review, we put together these EMT transcription factors and discussed their role in the process. We have also tried to focus on their mechanism of action, their inter-dependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type dependent manner.

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Section: Other Emt Tfsmentioning

confidence: 99%

Epithelial–mesenchymal transition and its transcription factors

et al. 2021

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“…The results of in vitro assays also support the involvement of BACH1 in the metastatic properties of cancer cells. Invasion and migration activities of PDAC cells, esophageal cancer cells, colon cancer cells, and ovarian cancer cells in vitro are reduced upon BACH1 knockdown ( 79 , 80 , 81 , 82 , 83 , 84 ). When overexpressed in colon or ovarian cancer cells, BACH1 enhanced tumor growth in transplanted mice, but metastasis was not investigated ( 81 ).…”

Section: Functions Of Bach1 In Cancer Metastasismentioning

confidence: 99%

“…When overexpressed in colon or ovarian cancer cells, BACH1 enhanced tumor growth in transplanted mice, but metastasis was not investigated ( 81 ). An increased expression of BACH1 was shown to be correlated with a poorer prognosis of patients with breast, pancreatic, colorectal, ovarian, and esophageal cancers as well as glioblastoma ( 79 , 80 , 81 , 84 , 85 , 86 ). Taken together, these observations indicate that cancer cells acquire metastatic potential when the activity of BACH1 is increased.…”

Section: Functions Of Bach1 In Cancer Metastasismentioning

confidence: 99%

“…Depending on these transcription factors, BACH1 is connected indirectly to additional downstream genes for the epithelial structures as well. The expression of E-cadherin gene CDH1 is low in cancer cells with a high BACH1 expression, and a reduced expression of CDH1 is dependent on BACH1 ( 79 , 80 , 84 ). Because FOXA1 directly activates the expression of CDH1 ( 88 ), FOXA1 may mediate the connection between BACH1 and CDH1 ( Fig.…”

Section: Functions Of Bach1 In Cancer Metastasismentioning

confidence: 99%

“…SNAI2 encodes an archetypal transcription factor driving EMT by repressing genes involved in cell–cell adhesion and promoting the stem cell function ( 95 , 96 , 97 ). SNAI2 is directly activated by BACH1 in PDAC, ovarian cancer, and esophageal squamous cell carcinoma cells ( 79 , 80 , 84 ), suggesting that the BACH1–SNAI2 axis likely contributes to the silencing of epithelial genes.

Figure 3 BACH1 GRNs for cancer cell progression.…”

Section: Functions Of Bach1 In Cancer Metastasismentioning

confidence: 99%

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The transcription factor BACH1 at the crossroads of cancer biology: From epithelial–mesenchymal transition to ferroptosis

Igarashi

Nishizawa

Saiki

et al. 2021

Journal of Biological Chemistry

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The progression of cancer involves not only the gradual evolution of cells by mutations in DNA but also alterations in the gene expression induced by those mutations and input from the surrounding microenvironment. Such alterations contribute to cancer cells' abilities to reprogram metabolic pathways and undergo epithelial-to-mesenchymal transition (EMT), which facilitate the survival of cancer cells and their metastasis to other organs. Recently, BTB and CNC homology 1 (BACH1), a heme-regulated transcription factor that represses genes involved in iron and heme metabolism in normal cells, was shown to shape the metabolism and metastatic potential of cancer cells. The growing list of BACH1 target genes in cancer cells reveals that BACH1 promotes metastasis by regulating various sets of genes beyond iron metabolism. BACH1 represses the expression of genes that mediate cell–cell adhesion and oxidative phosphorylation but activates the expression of genes required for glycolysis, cell motility, and matrix protein degradation. Furthermore, BACH1 represses FOXA1 gene encoding an activator of epithelial genes and activates SNAI2 encoding a repressor of epithelial genes, forming a feedforward loop of EMT. By synthesizing these observations, we propose a “two-faced BACH1 model”, which accounts for the dynamic switching between metastasis and stress resistance along with cancer progression. We discuss here the possibility that BACH1-mediated promotion of cancer also brings increased sensitivity to iron-dependent cell death (ferroptosis) through crosstalk of BACH1 target genes, imposing programmed vulnerability upon cancer cells. We also discuss the future directions of this field, including the dynamics and plasticity of EMT.

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The Cys‐Pro motifs in the intrinsically disordered regions of the transcription factor BACH1 mediate distinct and overlapping functions upon heme binding

2022

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The function of the transcription factor BACH1 is regulated by heme binding to multiple Cys‐Pro (CP) motifs within its intrinsically disordered regions. Here, biochemical analyses were conducted to reveal the individual functional roles of the CP motifs. Our findings revealed that four CP motifs in BACH1 individually contributed to the regulation of BACH1 activity by accepting heme in a five‐ and six‐coordination manner. The model structure around the bZip domain indicated that the CP motifs are in the N‐ and C‐terminal heme‐binding regions, which are approximately 9 nm apart, suggesting that spatial location is important for the individual function of the CP motifs. The presence of multiple CP motifs with distinct roles may ensure the multifaceted, strict regulation of BACH1 by heme.

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BACH1 promotes the progression of esophageal squamous cell carcinoma by inducing the epithelial–mesenchymal transition and angiogenesis

Cited by 20 publications

References 46 publications

Epithelial–mesenchymal transition and its transcription factors

Epithelial–mesenchymal transition and its transcription factors

The transcription factor BACH1 at the crossroads of cancer biology: From epithelial–mesenchymal transition to ferroptosis

The Cys‐Pro motifs in the intrinsically disordered regions of the transcription factor BACH1 mediate distinct and overlapping functions upon heme binding

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