Inhibition of Delta-like Ligand 4 enhances the radiosensitivity and inhibits migration in cervical cancer via the reversion of epithelial–mesenchymal transition

  title={Inhibition of Delta-like Ligand 4 enhances the radiosensitivity and inhibits migration in cervical cancer via the reversion of epithelial–mesenchymal transition},
  author={Shanshan Yang and Deyang Yu and Yuting Du and Le Wang and Lina Gu and Yunyan Zhang and Min Xiao},
  journal={Cancer Cell International},
Background Concurrent chemoradiotherapy is the common first-line treatment for patients with advanced cervical cancer. However, radioresistance remains a major clinical challenge, which results in recurrence and poor survival. Many studies have shown the potential of Delta-like Ligand 4 (DLL4) as a novel prognostic biomarker and therapeutic target in many solid tumors. Previously, we have found that high DLL4 expression in tumor cells may predict the pelvic lymph node metastasis and poor… 
Increased Angiogenin Expression Correlates With Radiation Resistance and Predicts Poor Survival for Patients With Nasopharyngeal Carcinoma
The results found the radioresistant function of ANG and proved the clinical prognostic significance of ANG, and the results could help predict radio-sensitivity and stratify high-risk patients or tumour recurrence.
Notch signaling in female cancers: a multifaceted node to overcome drug resistance
The main aim of this review is to provide strong evidence in support of Notch signaling inhibition as an effective strategy to evade or reverse resistance in female-specific cancers.
Radiotherapy resistance: identifying universal biomarkers for various human cancers
This review presents the state-of-the-art for the potential universal biomarkers correlated to the radioresistance and poor outcome in different cancers and describes radiores resistance biomarkers functionally attributed to DNA repair, signal transduction, hypoxia, and angiogenesis.
Cdc25B is transcriptionally inhibited by IER5 through the NF-YB transcription factor in irradiation-treated HeLa cells.
Findings indicate that IER5 is the transcriptional repressor that accelerates the downregulation of Cdc25B expression after irradiation.
A 25 Immune-Related Gene Pair Signature Predicts Overall Survival in Cervical Cancer
An IRGP prognostic signature of CC was successfully constructed, providing insights into immunotherapy for CC, and univariate and multivariate Cox regression analyses showed that the IRGP signature was an independent prognostic factor of overall survival.


The role of NRAGE subcellular location and epithelial–mesenchymal transition on radiation resistance of esophageal carcinoma cell
The results indicate that NRAGE subcellular localization is related to radiation resistance of esophageal carcinoma cell and EMT may be involved in NRAGESubcellular location.
MiR-181a confers resistance of cervical cancer to radiation therapy through targeting the pro-apoptotic PRKCD gene
The expression level of miR-181a in cervical cancer may serve as a biomarker for sensitivity to radiation therapy, and targeting miR -181a may represent a new approach to sensitizing cervical cancer to radiation treatment.
Influence of up-regulation of Notch ligand DLL4 on biological behaviors of human gastric cancer cells.
Observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.
DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer
The data indicate that high DLL4 expression predicts pelvic lymph node metastasis and poor survival in cervical cancer and may be a potential clinical diagnostic marker for patients with early-stage cervical cancer.
Endothelial Delta-like 4 (DLL4) promotes renal cell carcinoma hematogenous metastasis
The data suggest that RCC progression is caused in part by activated DLL4/Notch signaling, interaction of endothelium and cells, which can be therapeutically targeted.
DLL4 overexpression increases gastric cancer stem/progenitor cell self‐renewal ability and correlates with poor clinical outcome via Notch‐1 signaling pathway activation
DLL4 silencing inhibits GCSPC metastatic potential both in vitro and in vivo by impeding Notch‐1 signaling pathway activation, indicating that DLL4 may be a new potential therapeutic target.
E-Cadherin loss associated with EMT promotes radioresistance in human tumor cells.
  • J. Theys, B. Jutten, M. Vooijs
  • Biology, Medicine
    Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
  • 2011
The network of epithelial–mesenchymal transition: potential new targets for tumor resistance
This review highlights the potential key therapeutic targets of EMT linked with tumor aggressiveness, hypoxia, angiogenesis and cancer stem cells, emphasizing on an emerging EMT-associated NF-κB/HER2/STAT3 pathway in radioresistance of breast cancer stem Cells.
Epithelial-to-Mesenchymal Transition: A Mediator of Sorafenib Resistance in Advanced Hepatocellular Carcinoma.
Preclinical studies on the EMT mechanisms underlying resistance to sorafenib treatment are provided to facilitate rational development of combination therapies in the future to impact survival of patients with advanced HCC and how combination of sorafinib with EMT inhibitors could enhance the clinical response to sorAFenib, resulting in longer duration of responses.