Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma

Taylor, Chase J.; Loomans, Holli A.; Bras, Grégoire F. Le; Koumangoye, Rainelli; Romero-Morales, Alejandra I.; Quast, Laura L.; Zaika, Alexander; El–Rifai, Wael; Andl, Thomas; Andl, Claudia D.

doi:10.18632/oncotarget.5349

Cited by 28 publications

(15 citation statements)

References 58 publications

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“…We found a significant correlation between CHD1L expression and poor clinical outcome, independent of other characteristics. In addition, our results indicate that CHD1L expression is a potential novel prognostic marker for EC [ 26 – 28 ]. These results correspond to those of previous studies in other types of human cancers.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CHD1L is associated with poor survival and aggressive tumor biology in esophageal carcinoma

et al. 2017

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Esophageal carcinoma (EC) is a malignancy with high metastatic potential. Chromosomal helicase/ATPase DNA binding protein 1-like (CHD1L) gene is a newly identified oncogene located at Chr1q21, and it is amplified in many solid tumors. However, the status of CHD1L protein expression in EC and its clinical significance is uncertain. This study was designed to investigate the significance of CHD1L expression in human EC and its biological function in EC cells. The expression of CHD1L was examined by immunohistochemistry in 191 surgically resected ECs. The associations between CHD1L expression and clinical pathological parameters and the prognostic value of CHD1L were analyzed. Western blot analysis showed that CHD1L was overexpressed in EC cell lines. In addition, positive CHD1L expression was strongly related to advanced clinical stage (P<0.01), and lymph node metastasis (P<0.01) of EC. The Kaplan-Meier curve indicated that high expression of CHD1L may result in poor prognosis of EC patients (P<0.01), and multivariate analysis showed that CHD1L overexpression was an independent predictor of overall survival. Furthermore, suppression of CHD1L in EC cells increased apoptosis and decreased cell proliferation invasion ability. Our results suggest that CHD1L is a target oncogene with the potential to serve as a novel prognostic biomarker in EC pathogenesis.

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Section: Discussionmentioning

confidence: 99%

Overexpression of CHD1L is associated with poor survival and aggressive tumor biology in esophageal carcinoma

et al. 2017

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“…Activin, a member of the transforming growth factor-β (TGF-β) family, is a promigratory factor that is expressed in wounded tissues and promotes keratinocyte migration into the injured site [ 1 ]. Activin can also increase the in vitro migratory and invasive capacity of several epithelial cancer cell lines [ 2 , 3 ]. These results suggest that activin may promote metastatic progression of cancer, but this supposition has not been fully assessed.…”

Section: Introductionmentioning

confidence: 99%

Follistatin is a metastasis suppressor in a mouse model of HER2-positive breast cancer

et al. 2017

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BackgroundFollistatin (FST) is an intrinsic inhibitor of activin, a member of the transforming growth factor-β superfamily of ligands. The prognostic value of FST and its family members, the follistatin-like (FSTL) proteins, have been studied in various cancers. However, these studies, as well as limited functional analyses of the FSTL proteins, have yielded conflicting results on the role of these proteins in disease progression. Furthermore, very few have been focused on FST itself. We assessed whether FST may be a suppressor of tumorigenesis and/or metastatic progression in breast cancer.MethodsUsing publicly available gene expression data, we examined the expression patterns of FST and INHBA, a subunit of activin, in normal and cancerous breast tissue and the prognostic value of FST in breast cancer metastases, recurrence-free survival, and overall survival. The functional effects of activin and FST on in vitro proliferation, migration, and invasion of breast cancer cells were also examined. FST overexpression in an autochthonous mouse model of breast cancer was then used to assess the in vivo impact of FST on metastatic progression.ResultsExamination of multiple breast cancer datasets revealed that FST expression is reduced in breast cancers compared with normal tissue and that low FST expression predicts increased metastasis and reduced overall survival. FST expression was also reduced in a mouse model of HER2/Neu-induced metastatic breast cancer. We found that FST blocks activin-induced breast epithelial cell migration in vitro, suggesting that its loss may promote breast cancer aggressiveness. To directly determine if FST restoration could inhibit metastatic progression, we transgenically expressed FST in the HER2/Neu model. Although FST had no impact on tumor initiation or growth, it completely blocked the formation of lung metastases.ConclusionsThese data indicate that FST is a bona fide metastasis suppressor in this mouse model and support future efforts to develop an FST mimetic to suppress metastatic progression.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0857-y) contains supplementary material, which is available to authorized users.

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“…Our finding suggests that the differential expression of metalloproteinases related genes is important for EAC. The other top upregulated GO categories identified are collagen28, proteinaceous extracellular matrix and extracellular matrix part2930. Extracellular matrix interaction can be promoted by mucins – large o-glycoproteins, which are often overexpressed in cancer cells3132.…”

Section: Resultsmentioning

confidence: 99%

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

Peng

Guo

Chen

et al. 2017

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The incidence of esophageal adenocarcinoma (EAC) is rapidly rising in the United States and Western countries. In this study, we carried out an integrative molecular analysis to identify interactions between genomic and epigenomic alterations in regulating gene expression networks in EAC. We detected significant alterations in DNA copy numbers (CN), gene expression levels, and DNA methylation profiles. The integrative analysis demonstrated that altered expression of 1,755 genes was associated with changes in CN or methylation. We found that expression alterations in 84 genes were associated with changes in both CN and methylation. These data suggest a strong interaction between genetic and epigenetic events to modulate gene expression in EAC. Of note, bioinformatics analysis detected a prominent K-RAS signature and predicted activation of several important transcription factor networks, including β-catenin, MYB, TWIST1, SOX7, GATA3 and GATA6. Notably, we detected hypomethylation and overexpression of several pro-inflammatory genes such as COX2, IL8 and IL23R, suggesting an important role of epigenetic regulation of these genes in the inflammatory cascade associated with EAC. In summary, this integrative analysis demonstrates a complex interaction between genetic and epigenetic mechanisms providing several novel insights for our understanding of molecular events in EAC.

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Activin a signaling regulates cell invasion and proliferation in esophageal adenocarcinoma

Cited by 28 publications

References 58 publications

Overexpression of CHD1L is associated with poor survival and aggressive tumor biology in esophageal carcinoma

Overexpression of CHD1L is associated with poor survival and aggressive tumor biology in esophageal carcinoma

Follistatin is a metastasis suppressor in a mouse model of HER2-positive breast cancer

Integrated molecular analysis reveals complex interactions between genomic and epigenomic alterations in esophageal adenocarcinomas

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