STAT1 activation in squamous cell cancer of the oral cavity

Laimer, Klaus; Spizzo, Gilbert; Obrist, Peter; Gastl, Guenther; Brunhuber, Thomas; Schäfer, Georg; Norer, B; Rasse, Michael; Haffner, Michael C.; Doppler, Wolfgang

doi:10.1002/cncr.22813

Cited by 34 publications

(20 citation statements)

References 76 publications

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“…Laimer and colleagues (16) found that high levels of STAT1 in HNSCC tumor specimens correlated with improved survival in patients treated with adjuvant platinum-based chemotherapy, which is opposite the trend seen in our study. This study was similar to ours in terms of the number of patients, tumor characteristics such as anatomic subsite and stage, and method for dividing patients between high and low STAT1 staining groups.…”

Section: Discussioncontrasting

confidence: 99%

“…It is unclear, however, whether specific tumor biomarkers might help identify patients more likely to benefit from the combination of cisplatin, radiation and EGFR inhibitors. Two prior small clinical studies suggest that high levels of intratumoral STAT1 might be a favorable prognostic marker for HNSCC patients treated with chemotherapy (16, 17). To explore whether STAT1 might be a biomarker of response to cisplatin and EGFR inhibition, we obtained tumor specimens from patients with advanced, high-risk HNSCC treated with surgery followed by adjuvant radiation, cisplatin and panitumumab.…”

Section: Resultsmentioning

confidence: 99%

“…STAT1 -null, non-tumor cells are relatively resistant to cisplatin-induced cell death (11, 14), and antitumor efficacy of cisplatin may depend on adaptive immunity in HNSCC (15). Two small clinical trials suggest that high STAT1 staining in tumor specimens may be a good prognostic indicator in HNSCC patients treated with platinum-based chemotherapy (16, 17). …”

Section: Introductionmentioning

confidence: 99%

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STAT1 Activation Is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells

Schmitt

Trivedi

Ferris

2015

Molecular Cancer Therapeutics

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Cisplatin is a cytotoxic chemotherapeutic drug frequently used to treat many solid tumors, including head and neck squamous cell carcinoma (HNSCC). EGFR inhibitors have also shown efficacy as alternatives to cisplatin in some situations. However, large clinical trials have shown no added survival benefit from the use of these two drugs in combination. Possible explanations for this include overlapping downstream signaling cascades. Using in vitro studies, we tested the hypothesis that cisplatin and EGFR inhibitors rely on the activation of the tumor suppressor STAT1, characterized by its phosphorylation at serine (S727) or tyrosine (Y701) residues. Cisplatin consistently increased the levels of p-S727-STAT1, and STAT1 siRNA knockdown attenuated cisplatin-induced cell death. EGFR stimulation also activated p-S727-STAT1 and p-Y701-STAT1 in a subset of cell lines, whereas EGFR inhibitors alone decreased levels of p-S727-STAT1 and p-Y701-STAT1 in these cells. Contrary to our hypothesis, EGFR inhibitors added to cisplatin treatment caused variable effects among cell lines, with attenuation of p-S727-STAT1 and enhancement of cisplatin-induced cell death in some cells and minimal effect in other cells. Using HNSCC tumor specimens from a clinical trial of adjuvant cisplatin plus the anti-EGFR antibody panitumumab, higher intratumoral p-S727-STAT1 appeared to correlate with worse survival. Together, these results suggest that cisplatin-induced cell death is associated with STAT1 phosphorylation, and the addition of anti-EGFR therapy to cisplatin has variable effects on STAT1 and cell death in HNSCC.

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Section: Discussioncontrasting

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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STAT1 Activation Is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells

Schmitt

Trivedi

Ferris

2015

Molecular Cancer Therapeutics

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“…Aberrant activation of STAT1 has frequently been found in various cancers, such as head and neck cancer [75]. A similar STAT1 activation status was detected in patients with OSCC [76]. In this study, STAT1 displayed a significant association with OC using both the RWR-based and SP-based methods, and this molecular marker could help in guiding diagnostic and therapeutic decisions in patients with OC.…”

Section: Discussionsupporting

confidence: 62%

An integrated method for the identification of novel genes related to oral cancer

Lei¹,

Yang²,

Xing³

et al. 2017

PLoS ONE

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Cancer is a significant public health problem worldwide. Complete identification of genes related to one type of cancer facilitates earlier diagnosis and effective treatments. In this study, two widely used algorithms, the random walk with restart algorithm and the shortest path algorithm, were adopted to construct two parameterized computational methods, namely, an RWR-based method and an SP-based method; based on these methods, an integrated method was constructed for identifying novel disease genes. To validate the utility of the integrated method, data for oral cancer were used, on which the RWR-based and SP-based methods were trained, thereby building two optimal methods. The integrated method combining these optimal methods was further adopted to identify the novel genes of oral cancer. As a result, 85 novel genes were inferred, among which eleven genes (e.g., MYD88, FGFR2, NF-κBIA) were identified by both the RWR-based and SP-based methods, 70 genes (e.g., BMP4, IFNG, KITLG) were discovered only by the RWR-based method and four genes (L1R1, MCM6, NOG and CXCR3) were predicted only by the SP-based method. Extensive analyses indicate that several novel genes have strong associations with cancers, indicating the effectiveness of the integrated method for identifying disease genes.

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“…Increased STAT1 expression and high STAT1 activation (p-STAT1 protein levels) were related to a favorable prognosis in colorectal carcinoma [10,11], oral squamous cell carcinoma [12], as well as in breast cancer [13]. In addition, Sun et al [14] observed that overexpression of STAT1 was inversely related to malignant behaviors (lymph node metastasis, tumor dedifferentiation, advanced stage) of pancreatic cancer.…”

Section: Discussionmentioning

confidence: 99%

The prognostic values of signal transducers activators of transcription family in ovarian cancer

Sheng

Zhao

et al. 2017

Bioscience Reports

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Signal transducer and activator of transcription (STAT), a family of latent cytoplasmic transcription factors, are composed of seven identified members (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). STATs are associated with several biological processes such as cell proliferation, invasion, and metastasis in various cancer types. In addition, the STAT family has been well studied as a prognostic predictor for a considerable number of solid tumors. However, the prognostic value of the STAT family in ovarian cancer patients remains unclear. In our present study, we intend to access the prognostic roles of the STAT family in ovarian carcinoma through the ‘Kaplan–Meier plotter’ (KM plotter) online database, which collected gene expression data and survival information (overall survival (OS)) from a total of 1582 ovarian cancer patients. Our results show that high mRNA expression of STAT1, STAT4, STAT5a, STAT5b, and STAT6, are correlated to a better OS of ovarian cancer patients, especially the high level of STAT1 and STAT4 are significantly related to a favorable OS for serous ovarian cancer patients. We further accessed the prognostic roles of individual STATs in other clinicopathological features, such as pathological grades, clinical stages, and TP53 mutation, and found that these genes indicate a favorable prognosis especially for late stage, poor differentiation, and TP53 mutated ovarian cancer patients. In conclusion, these results suggest that the STAT family plays a significant prognostic role in ovarian carcinoma and individual STATs, except STAT2 and STAT3, may act as favorable prognostic markers in ovarian cancer.

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STAT1 activation in squamous cell cancer of the oral cavity

Cited by 34 publications

References 76 publications

STAT1 Activation Is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells

STAT1 Activation Is Enhanced by Cisplatin and Variably Affected by EGFR Inhibition in HNSCC Cells

An integrated method for the identification of novel genes related to oral cancer

The prognostic values of signal transducers activators of transcription family in ovarian cancer

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