Forkhead box protein A1 confers resistance to transforming growth factor‐β‐induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation

Hirata, Kensuke; Takakura, Yuki; Shibazaki, Misato; Morii, Mariko; Honda, Takeshi; Oshima, Motohiko; Aoyama, Kazumasa; Iwama, Atsushi; Nakayama, Yuji; Takano, Hiroyuki; Yamaguchi, Naoto; Yamaguchi, Noritaka

doi:10.1002/jcb.27551

Cited by 5 publications

(4 citation statements)

References 27 publications

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“…Some studies demonstrated that forkhead box protein A1 (FOXA1), a member of forkhead box gene superfamily, inhibits apoptosis in cancer cells [82,83]. Consistent with these in vitro data, Ren et al observed that gastric cancer patients with high expression of FOXA1 had poorer five-year overall survival [84].…”

Section: A Multitude Of Molecules Regulate Apoptosis and Hippo-yapmentioning

confidence: 89%

The Ambivalent Function of YAP in Apoptosis and Cancer

Zhang

Abdelrahman

Vollmar

et al. 2018

IJMS

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Yes-associated protein, a core regulator of the Hippo-YAP signaling pathway, plays a vital role in inhibiting apoptosis. Thus, several studies and reviews suggest that yes-associated protein is a good target for treating cancer. Unfortunately, more and more evidence demonstrates that this protein is also an essential contributor of p73-mediated apoptosis. This questions the concept that yes-associated protein is always a good target for developing novel anti-cancer drugs. Thus, the aim of this review was to evaluate the clinical relevance of yes-associated protein for cancer pathophysiology. This review also summarized the molecules, processes and drugs, which regulate Hippo-YAP signaling and discusses their effect on apoptosis. In addition, issues are defined, which should be addressed in the future in order to provide a solid basis for targeting the Hippo-YAP signaling pathway in clinical trials.

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Section: A Multitude Of Molecules Regulate Apoptosis and Hippo-yapmentioning

confidence: 89%

The Ambivalent Function of YAP in Apoptosis and Cancer

Zhang

Abdelrahman

Vollmar

et al. 2018

IJMS

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“…However, these approaches lack efficacy. In addition, the understanding of the molecular etiology of BC progression and development is poor [5]. Thus, it is crucial to explore innovative pathways and genes related to BC progression, along with the clinical outcome of patient therapy.…”

Section: Introductionmentioning

confidence: 99%

High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells

Wang

Chen

et al. 2019

Med Sci Monit

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Background High-mobility group box 1 (HMGB1) is an essential contributor towards initiation and progression of many kinds of cancers. Nevertheless, our understanding of the molecular etiology of HMGB1-modulated vasculogenesis, as well as invasion, of breast cancer is poor. This study explored HMGB1 expression in breast cancer and its role in the development and spread of malignancy. Material/Methods We enrolled 15 patients with breast cancer who received primary surgery at the Department of Thyroid and Breast Surgery in our hospital. HMGB1 was recorded and analyzed. Results Our investigation successfully proves that HMGB1 is upregulated in breast cancer tissues in comparison to the surrounding non-malignant tissues. HMGB1 enhanced vessel formation in breast cancer tissues by regulating hypoxia-inducible factor 1 (HIF-1α), which in turn upregulates the expression of VEGF. Furthermore, HMGB1-mediated upregulation of HIF-1α relies on its ability to stimulate the phosphatidylinositol 3-kinase (PI3K) pathway to reinforce AKT subunit phosphorylation. HMGB1 overexpression reinforces the vasculogenesis in malignancies not only in vivo but also in vitro . Additionally, shRNA knockdown of HMGB1 prohibited the vessel-forming and invasive capabilities, downregulated VEGF and HIF-1α, and suppressed AKT phosphorylation in breast cancer cells. Most importantly, PI3K/AKT axis suppression eliminated the effect of HMGB1-modulated vascularization and invasion in breast cancer cells. Conclusions Our research indicates that HMGB1 serves as a crucial regulator of malignant cell-modulated vessel formation and is involved in the development of malignancy. Our findings indicate that HMGB1 is a promising target for breast cancer treatment.

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“…Repeating the CUT&RUN experiments under optimized experimental conditions should help in investigating this hypothesis further. Alternatively, "DNA-free" FOXA1 might localize to the cytoplasm and inhibit nuclear translocation of other TFs to promote cell death [88].…”

Section: Discussionmentioning

confidence: 99%

Investigating the Role of Chromatin Remodeler FOXA1 in Ferroptotic Cell Death

Logie

Maes

Meenen

et al. 2021

Preprint

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Ferroptosis is a lipid peroxidation-dependent mechanism of regulated cell death known to suppress tumor proliferation and progression. Although several genetic and protein hallmarks have been identified in ferroptotic cell death, it remains challenging to fully characterize ferroptosis signaling pathways and to find suitable biomarkers. Moreover, changes taking place in the epigenome of ferroptotic cells remain poorly studied. In this context, we aimed to investigate the role of chromatin remodeler forkhead box protein A1 (FOXA1) in RSL3-treated multiple myeloma cells because, similar to ferroptosis, this transcription factor has been associated with changes in the lipid metabolism, DNA damage, and epithelial-to-mesenchymal transition (EMT). RNA sequencing and Western blot analysis revealed that FOXA1 expression is consistently upregulated upon ferroptosis induction in different in vitro and in vivo disease models. In silico motif analysis and transcription factor enrichment analysis further suggested that ferroptosis-mediated FOXA1 expression is orchestrated by specificity protein 1 (Sp1), a transcription factor known to be influenced by lipid peroxidation. Remarkably, FOXA1 upregulation in ferroptotic myeloma cells did not alter hormone signaling or EMT, two key downstream signaling pathways of FOXA1. CUT&RUN genome-wide transcriptional binding site profiling showed that GPX4-inhibition by RSL3 triggered loss of binding of FOXA1 to pericentromeric regions in multiple myeloma cells, suggesting that this transcription factor is possibly involved in genomic instability, DNA damage, or cellular senescence under ferroptotic conditions.

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Forkhead box protein A1 confers resistance to transforming growth factor‐β‐induced apoptosis in breast cancer cells through inhibition of Smad3 nuclear translocation

Cited by 5 publications

References 27 publications

The Ambivalent Function of YAP in Apoptosis and Cancer

The Ambivalent Function of YAP in Apoptosis and Cancer

High-Mobility Group Box 1 (HMGB1) Promotes Angiogenesis and Tumor Migration by Regulating Hypoxia-Inducible Factor 1 (HIF-1α) Expression via the Phosphatidylinositol 3-Kinase (PI3K)/AKT Signaling Pathway in Breast Cancer Cells

Investigating the Role of Chromatin Remodeler FOXA1 in Ferroptotic Cell Death

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