Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients

Pavón, Miguel Ángel; Arroyo‐Solera, Irene; Gabriel, Marta Tellez; León, Xavier; Virós, David; López, Montserrat; Gallardo, Alberto; Céspedes, María Virtudes; Casanova, Isolda; López‐Pousa, Antonio; Mangues, María Antònia; Quer, Miquel; Barnadas, Agustí; Mangues, Ramón

doi:10.18632/oncotarget.5032

Cited by 71 publications

(86 citation statements)

References 60 publications

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“…SerpinE1 overexpression also inhibited the activation of caspase‐3 while reducing the number of apoptotic figures at the primary tumor site in vivo. These results are consistent with previous in vitro findings from our group in which serpinE1 overexpression decreased cisplatin‐induced apoptosis by activating PI3K/Akt pathway in HNSCC cells . In agreement with our results, studies conducted in tumor cell lines other than HNSCC reported that serpinE1 can reduce spontaneous and induced apoptosis by blocking Fas/FasL or activating PI3K/Akt survival pathway …”

Section: Discussionsupporting

confidence: 93%

“…74BserpE1up was obtained by transduction of the 74BGFPLuc HNSCC cell line with the serpinE1‐expressing lentiviral vector (pFUGW_serpinE1) as described previously . 74BGFPLuc and 74BserpE1up cell lines were cultured in Dulbecco's Modified Eagle's Medium (DMEM) containing 10% Fetal Bovine Serum (FBS), 100 U/mL streptomycin/penicillin and 2 mM glutamine (Thermo Fisher Scientific, Waltham, Massachusetts) and maintained in a humidified atmosphere at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…SerpinE1 is the main regulator of the plasminogen activator system, which plays a key role to control tumor cell migration and the extracellular matrix remodeling, two essential mechanisms for the acquisition of a metastatic phenotype . Previously, we described that serpinE1 expression promotes migration and reduces apoptosis in HNSCC cell lines . Nevertheless, in vitro models have some restrictions to study 3D growth, invasiveness, or dissemination capacity of tumor cells …”

Section: Introductionmentioning

confidence: 99%

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Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma

et al. 2018

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Background Serpin Family E Member 1 (SerpinE1) overexpression associates with poor clinical outcome in head and neck squamous cell carcinoma (HNSCC) patients. This study analyzed the role of serpinE1 in HNSCC dissemination. Methods We studied the phenotypic characteristics and dissemination of HNSCC cells overexpressing serpinE1 using an orthotopic model and the association between serpinE1 overexpression and clinicopathological variables in patients included in The Cancer Genome Atlas database. Results SerpinE1 overexpression increased proliferation, tumor budding, and the stromal component, while inhibiting apoptosis in primary tumors. It also enhanced the affectation and metastatic growth in lymph nodes, and the dispersion and growth of metastatic foci in the lung. High serpinE1 expression was associated with larger tumor size, undifferentiated tumors, lymph node metastasis, extracapsular spread, and the presence of perineural and angiolymphatic invasion. Conclusion SerpinE1 overexpression promotes tumor aggressiveness and metastatic dissemination to lymph nodes and lung consistently with its association with poor outcome in HNSCC patients.

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Section: Discussionsupporting

confidence: 93%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma

et al. 2018

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“…A recent study shows that overexpression of THBS2 correlated with poor OS and RFS in CRC patients, which is consistent with our results 21. SERPINE1 expression has been shown to be associated with tumor cell migration and invasion through the activation of the PI3K-Akt pathway 22–24. Furthermore, SERPINE1 pro-migratory effect has been associated with LRP1 interaction, which in turn stimulates the Jak/Stat pathway 25.…”

Section: Discussionsupporting

confidence: 91%

Computational analysis of mRNA expression profiles identifies a novel triple-biomarker model as prognostic predictor of stage II and III colorectal adenocarcinoma patients

Cheng¹,

Hu²,

Chen³

et al. 2018

CMAR

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IntroductionAlthough remarkable progress has been made to determine the prognosis of patients with colorectal cancer (CRC), it is inadequate to identify the subset of high-risk TNM stage II and stage III patients that have a high potential of developing tumor recurrence and may experience death. In this study, we aimed to develop biomarkers as a prognostic signature for the clinical outcome of CRC patients with stage II and stage III.Materials and methodsWe performed a systematic and comprehensive discovery step to identify recurrence-associated genes in CRC patients through publicly available GSE41258 (n=253) and GSE17536 (n=107) datasets. We subsequently determined the prognostic relevance of candidate genes in stage II and III patients and developed a triple-biomarker for predicting RFS in GSE17536, which was later validated in an independent cohort GSE33113 dataset (n=90).ResultsBased upon mRNA expression profiling studies, we identified 45 genes which differentially expressed in recurrent vs non-recurrent CRC patients. By using Cox proportional hazard models, we then developed a triple-marker model (THBS2, SERPINE1, and FN1) to predict prognosis in GSE17536, which successfully identified poor prognosis in stage II and stage III, particularly high-risk stage II CRC patients.DiscussionNotably, we found that our triple-marker model once again predicted recurrence in stage II patients in GSE33113. Kaplan–Meier survival analysis demonstrated that patients with high scores have a poor outcome compared to those with low scores. Our triple-marker model is a reliable predictive tool for determining prognosis in CRC patients with stage II and stage III, and might be able to identify high-risk patients that are candidates for more targeted personalized clinical management and surveillance.

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“…It reacts directly to integrin, uPA-uPAR and ECM, causing to invade and migrate to surrounding and distance [10, 24]. Meanwhile, SERPINE1 has been considered as biomarker related to poorer prognosis in CRC [11].…”

Section: Discussionmentioning

confidence: 99%

Integrated analysis of genes associated with poor prognosis of patients with colorectal cancer liver metastasis

et al. 2017

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Colorectal cancer (CRC) is one of the most common malignances in the gut. Liver is the most common metastasis site of CRC. This study focuses on the primary CRC and its liver metastasis, aiming to discover several liver metastasis related genes and provide therapeutic candidates. We compared gene expression patterns among the groups of normal colorectal mucosa, primary tumor and the liver metastasis using a CRC gene expression dataset. 84 genes were found to be upregulated in both primary tumor and liver metastases. Function enrichment analysis indicated that these genes are enriched in pathways such as chemotaxis, coagulation and lipid metabolism which are crucial in multi-step cancer metastasis. Gene network analysis identified several important hub genes that may be involved in carcinogenesis and liver metastasis. Then we used a validation dataset containing 562 CRC samples with detailed clinical information, to screen prognostic biomarkers for overall survival (OS) and relapse free survival (RFS). Finally, overexpression of THBS2 (thrombospondin 2), INHBB (inhibin, beta B) and BGN (biglycan) were proved to be correlated with poor OS and RFS. In conclusion, this study indicated that chemotaxis, coagulation and lipid metabolism might play critical roles in the processes of carcinogenesis and liver metastasis. THBS2, INHBB and BGN are prognostic markers and potential therapeutic targets for CRC.

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Enhanced cell migration and apoptosis resistance may underlie the association between high SERPINE1 expression and poor outcome in head and neck carcinoma patients

Cited by 71 publications

References 60 publications

Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma

Effect of serpinE1 overexpression on the primary tumor and lymph node, and lung metastases in head and neck squamous cell carcinoma

Computational analysis of mRNA expression profiles identifies a novel triple-biomarker model as prognostic predictor of stage II and III colorectal adenocarcinoma patients

Integrated analysis of genes associated with poor prognosis of patients with colorectal cancer liver metastasis

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