Opposite roles of <i>FOXA1</i> and <i>NKX2‐1</i> in lung cancer progression

Deutsch, Lena; Wrage, Michaela; Koops, Susann; Glatzel, Markus; Uzunoglu, Faik G; Kutup, Asad; Hinsch, Andrea; Sauter, Guido; Izbicki, Jakob R.; Pantel, Klaus; Wikman, Harriet

doi:10.1002/gcc.21950

Cited by 27 publications

(25 citation statements)

References 39 publications

(53 reference statements)

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“…Finally, FOXA1 and FOXA2 are general transcriptional regulators, involved in opening the chromatin to make DNA accessible to the entry of other regulators3132. They are both missregulated in several malignancies3334353637. While FOXA1 is both recurrently mutated and FM biased in BRCA, FOXA2 is recurrently mutated and FM biased in UCEC and recurrently mutated and CLUST biased in the pan-cancer analysis.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive identification of mutational cancer driver genes across 12 tumor types

Tamborero

González-Pérez

Perez-Llamas

et al. 2013

Sci Rep

468

464

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With the ability to fully sequence tumor genomes/exomes, the quest for cancer driver genes can now be undertaken in an unbiased manner. However, obtaining a complete catalog of cancer genes is difficult due to the heterogeneous molecular nature of the disease and the limitations of available computational methods. Here we show that the combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes. We provide a list of 291 high-confidence cancer driver genes acting on 3,205 tumors from 12 different cancer types. Among those genes, some have not been previously identified as cancer drivers and 16 have clear preference to sustain mutations in one specific tumor type. The novel driver candidates complement our current picture of the emergence of these diseases. In summary, the catalog of driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis.

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Section: Resultsmentioning

confidence: 99%

Comprehensive identification of mutational cancer driver genes across 12 tumor types

Tamborero

González-Pérez

Perez-Llamas

et al. 2013

Sci Rep

468

464

View full text Add to dashboard Cite

show abstract

“…The genomic region encompassing the FOXA1 gene (14q21.1) is amplified in a range of cancers (Yasui et al, 2001; Lin et al, 2002; Nucera et al, 2009; Deutsch et al, 2012) and there is increasing evidence this also occurs in prostate and breast cancer. FOXA1 amplification in prostate cancer was identified from the profiling of eight systemic metastatic tumors in a range of organs from six unrelated patients.…”

Section: Foxa1 Copy Number Alterationsmentioning

confidence: 99%

FOXA1 mutations in hormone-dependent cancers

2013

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The forkhead protein, FOXA1, is a critical interacting partner of the nuclear hormone receptors, oestrogen receptor-α (ER) and androgen receptor (AR), which are major drivers of the two most common cancers, namely breast and prostate cancer. Over the past few years, progress has been made in our understanding of how FOXA1 influences nuclear receptor function, with both common and distinct roles in the regulation of ER or AR. Recently, another level of regulation has been described, with the discovery that FOXA1 is mutated in 1.8% of breast and 3–5% prostate cancers. In addition, a subset of both cancer types exhibit amplification of the genomic region encompassing the FOXA1 gene. Furthermore, there is evidence of somatic changes that influence the DNA sequence under FOXA1 binding regions, which may indirectly influence FOXA1-mediated regulation of ER and AR activity. These recent observations provide insight into the heterogeneity observed in ER and AR driven cancers.

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“…Initially, FOXA1 was identified in the liver and has been reported to be a transcriptional regulator of transthyretin (TTR) and α1-antitrypsin (α1-AT) (17). High levels of FOXA1 have been reported in lung cancer, thyroid carcinoma, esophageal squamous cell carcinoma and prostate cancer (18)(19)(20)(21), in addition to breast cancer (22). Notably, the current literature shows that the expression of FOXA1 is inversely proportional to that of miR-204 in breast cancer; when FOXA1 is highly expressed, miR-204 is expressed at low levels.…”

Section: Introductionmentioning

confidence: 99%

miR-204 regulates the biological behavior of breast cancer MCF-7 cells by directly targeting FOXA1

et al. 2017

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Abstract. MicroRNAs (miRNAs) are short, non-proteincoding RNAs and transcripts that are 18-24 nt in length. miR-204 was first identified as an anti-oncogene and is reported to be downregulated in non-small cell lung cancer, glioma, gastric and thyroid cancer. Recent studies have proposed that a low level of miR-204 expression is associated with tumor progression and disease outcome in breast cancer. Forkhead box A1 (FOXA1), a transcription factor, plays a crucial role in breast cancer and has been predicted as a target of miR-204. In the present study, we integrated the results of microarray analyses of breast cancer tissues obtained from an online database with our own determination of the expression of miR-204 in breast cancer MCF-7 cells using real-time qPCR (RT-qPCR). The proliferative capacity of the cells was assessed using MTT assays, and cell mobility and invasiveness were evaluated using cell migration and invasion assays, respectively. Flow cytometry was used to analyze apoptosis. FOXA1 levels were detected using RT-qPCR and western blot analysis. Luciferase assays were performed to confirm that FOXA1 is directly targeted by miR-204. The results showed that miR-204 was downregulated in breast cancer cells, and we found that miR-204 was expressed at a lower level in MCF-7 cells than that observed in normal breast epithelial HBL-100 cells. Overexpression of miR-204 inhibited cell proliferation, migration and invasion and promoted apoptosis. Western blot analysis revealed that the expression of FOXA1 at the protein level was significantly reduced after cells were transfected with miR-204-expressing viruses. Luciferase assays demonstrated that FOXA1 is a direct target of miR-204, which binds to FOXA1 in a complementary region. In conclusion, miR-204 regulates the biological behavior of breast cancer cells, including cell proliferation, invasion, metastasis and apoptosis, by directly targeting FOXA1. Thus, miR-204 may act as a tumor-suppressor, and the results of the present study provide a reference for future research into the potential mechanisms underlying breast cancer progression.

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Opposite roles of FOXA1 and NKX2‐1 in lung cancer progression

Cited by 27 publications

References 39 publications

Comprehensive identification of mutational cancer driver genes across 12 tumor types

Comprehensive identification of mutational cancer driver genes across 12 tumor types

FOXA1 mutations in hormone-dependent cancers

miR-204 regulates the biological behavior of breast cancer MCF-7 cells by directly targeting FOXA1

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