Steering of carcinoma progression by the YIN/YANG interaction of STAT1/STAT3

Friedrich, Karlheinz; Dolznig, Helmut; Han, Xiaonan; Moriggl, Richard

doi:10.5582/bst.2016.01250

Cited by 29 publications

(23 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…IL-6 increased cell viability in our experimental setting, but is not known to be involved in the acquisition of a mesenchymal phenotype. IL-6 activates proinflammatory-signaling pathways in epithelial cancers and leads to cancer progression, metastasis and therapy resistance through activation of pro-survival signals [ 46 – 49 ]. The effects of CM and IL-6 on cell viability imply that observed changes in cell viability are not caused by the acquisition of a mesenchymal phenotype (EMT), but rather an additional effect of EMC in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

et al. 2017

View full text Add to dashboard Cite

ObjectiveEpithelial-mesenchymal crosstalk (EMC) contributes to tumor progression, chemoresistance and acquisition of a mesenchymal phenotype (EMT) of cancer cells. This study aims to investigate the effects of EMC on radioresistance in head and neck squamous cell carcinoma (HNSCC) cells.MethodsIn tumor cell lines, the response of HNSCC cells, stimulated with EMC conditioned medium (CM), to irradiation was evaluated with viability and clonogenic assays. Dose modifying factors (DMF) were calculated from the results of clonogenic assays. Potential pathways involved in radioresistance were analyzed with quantitative Real-Time PCR and western blot.ResultsCM significantly reduced the doubling time of SCC-25 cells (from 32.8 hours to 16.8 hours, p=0.0001) and Detroit 562 cells (from 88.5 hours to 29.6 hours, p=0.014). Further it increased clonogenic survival after irradiation. The DMF of CM was 2.04 ± 0.43 (mean ± standard deviation) for SCC-25 cells (p=0.015) and 2.14 ± 0.34 for Detroit 562 cells (p=0.008). Treatment with CM more than tripled the ERCC1 and survivin gene expression in SCC-25 cells.ConclusionEMC induced pathways involved in cell survival and DNA repair and led to increased radioresistance in HNSCC cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

et al. 2017

View full text Add to dashboard Cite

show abstract

“…5 ). Promoters of interferon-stimulated MHC class I related genes are targets for STAT1, while STAT3 is known to interfere with transcription by sequestering STAT1 in the cytoplasm through heterodimerization (Friedrich et al, 2017; Nivarthi et al, 2016; Stancato et al, 1996). We hypothesize that the endogenous tonic interferon-STAT-MHC class I axis in DFTD is disrupted due to high STAT3 action promoting cancer cell proliferation, survival and invasion.…”

Section: Discussionmentioning

confidence: 99%

The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

Kosack

Wingelhofer

Popa

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

1The marsupial Tasmanian devil (Sarcophilus harrisii) faces extinction due to transmissible devil 2 facial tumor disease (DFTD). To unveil the molecular underpinnings of DFTD, we designed an 3 approach that combines sensitivity to drugs with an integrated systems-biology characterization. 4 Sensitivity to inhibitors of the ERBB family of receptor tyrosine kinases correlated with their 5 overexpression, suggesting a causative link. Proteomic and DNA methylation analyses revealed 6 tumor-specific signatures linked to oncogenic signaling hubs including evolutionary conserved 7 STAT3. Indeed, ERBB inhibition blocked phosphorylation of STAT3 and arrested cancer cells. 8 Pharmacological blockade of ERBB signaling prevented tumor growth in a xenograft model and 9 resulted in recovery of MHC class I gene expression. This link between the hyperactive ERBB-10

show abstract

“…Indeed, more site-specific analyses, performed by both Camp et al [86] and Davison et al [87], revealed greater accessibility of specific transcription factor binding sites in conventional mice. Both groups identified an upregulation in the accessibility of binding sites for transcription factors in the STAT (signal transducer and activator of transcription), IRF (interferon regulatory factor), and ETS (e26 transformation specific) families, each of which has been implicated in CRC progression [88][89][90]. Furthermore, many of these transcription factors were also identified by Richards and colleagues [91] as being differentially expressed after co-culture of CECs with gut bacteria.…”

Section: The Gut Microbiome and Chromatin Structurementioning

confidence: 99%

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

2019

View full text Add to dashboard Cite

In recent years, the number of studies investigating the impact of the gut microbiome in colorectal cancer (CRC) has risen sharply. As a result, we now know that various microbes (and microbial communities) are found more frequently in the stool and mucosa of individuals with CRC than healthy controls, including in the primary tumors themselves, and even in distant metastases. We also know that these microbes induce tumors in various mouse models, but we know little about how they impact colon epithelial cells (CECs) directly, or about how these interactions might lead to modifications at the genetic and epigenetic levels that trigger and propagate tumor growth. Rates of CRC are increasing in younger individuals, and CRC remains the second most frequent cause of cancer-related deaths globally. Hence, a more in-depth understanding of the role that gut microbes play in CRC is needed. Here, we review recent advances in understanding the impact of gut microbes on the genome and epigenome of CECs, as it relates to CRC. Overall, numerous studies in the past few years have definitively shown that gut microbes exert distinct impacts on DNA damage, DNA methylation, chromatin structure and non-coding RNA expression in CECs. Some of the genes and pathways that are altered by gut microbes relate to CRC development, particularly those involved in cell proliferation and WNT signaling. We need to implement more standardized analysis strategies, collate data from multiple studies, and utilize CRC mouse models to better assess these effects, understand their functional relevance, and leverage this information to improve patient care.

show abstract

Steering of carcinoma progression by the YIN/YANG interaction of STAT1/STAT3

Cited by 29 publications

References 47 publications

Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease

Impact of the gut microbiome on the genome and epigenome of colon epithelial cells: contributions to colorectal cancer development

Contact Info

Product

Resources

About