Abstract
Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-β3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-β3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-β3/SMAD-mediated EMT of CRC cells.
Highlights
Colorectal cancer (CRC) is the third most common cancer worldwide and remains a leading cause of cancerrelated deaths
Cox regression analysis revealed that Decoy receptor 3 (DcR3) expression, lymph node metastasis, age and infiltration were recognized as independent prognostic factors in this study (Supplementary Table S2)
DcR3 has attracted extensive www.impactjournals.com/oncotarget attention because its aberrant expression has been detected in various types of malignant tumors, especially hepatocellular carcinoma [12], pancreatic carcinoma [27], nasopharyngeal carcinoma [9], ovarian cancer [28], gastric carcinoma [29] and glioblastoma [30]
Summary
Colorectal cancer (CRC) is the third most common cancer worldwide and remains a leading cause of cancerrelated deaths. Surgical techniques and adjuvant therapy have improved, the overall survival of patients with CRC has not improved dramatically [1,2,3,4]. There is an acute need to identify new biomarkers that are capable of distinguishing between patients with poor and good prognoses. Dysregulated DcR3 expression plays an important role in tumorigenesis, metastasis and immune suppression in pancreatic head cancer [6], breast cancer [7], bladder urothelial carcinoma [8], nasopharyngeal carcinoma [9], renal carcinoma [10], glioma [11] and hepatocellular carcinoma [12, 13]. The contribution of DcR3 to CRC and the molecular basis for this contribution have not been fully elucidated
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