Overexpression and Clinicopathological Contribution of DcR3 in Bladder Urothelial Carcinoma Tissues

Jiang, Yi‑Qiang; Tang, Zhong; Dang, Yi‐Wu; Zou, Ling-Song; Yang, Liu; Yang, Xia; Chen, Gang

doi:10.7314/apjcp.2014.15.21.9137

Cited by 9 publications

(7 citation statements)

References 29 publications

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“…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]. However, the contribution of DcR3 to CRC and the molecular basis for this contribution have not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC

et al. 2016

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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.

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Section: Introductionmentioning

confidence: 99%

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC

et al. 2016

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“…DcR3/TNFRSF6B also protects against apoptosis because it can neutralize the cytotoxic ligands TNFS14/LIGHT, TNFSF15 and TNFSF6/FASL. Higher DcR3 expression was related to the status of invasion, lymph node metastasis and recurrence in bladder urothelial carcinoma [52]. Overexpression of DcR3 was found in bladder urothelial carcinomas and cell lines, with significant elevation as compared to normal bladder tissues and negatively correlated with caspase-3 and positively associated with Bcl-2, VEGF, and p53.…”

Section: Tumor Necrosis Factor-related Decoy Receptorsmentioning

confidence: 89%

The role of the TNF receptors and apoptosis inducing ligands in tumor growth

Minchenko¹,

Tsymbal²,

Minchenko³

et al. 2016

Ukr.Biochem.J.

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Tumor necrosis factor (TNF) superfamily receptors and TNF apoptosis inducing ligands play an important role in the realization of TNF function and control tumor growth. The TNF-related pathways are controlled by endoplasmic reticulum stress signaling, which has a crucial role in the control of cell proliferation and tumor growth. Furthermore, the inhibition of IRE1 (inositol requiring enzyme-1), which is a central mediator of endoplasmic reticulum stress sand mainly responsible for cell proliferation and apoptosis, leads to suppression of tumor growth through specific changes in the expression of genes encoding transcription factors, tumor suppressors, angiogenesis and apoptosis related proteins, including TNF superfamily receptors and TNF apoptosis inducing ligands. Therefore, changes in the expression level of TNF-related genes encoding TNF superfamily receptors and apoptosis inducing ligands possibly reflect metabolic reprogramming of cancer cells upon inhibition of IRE1-mediated endoplasmic reticulum stress signaling and correlate with suppression of glioma cell proliferation.

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“…DcR3 is expressed highly in a wide variety of tumors such as gastric cancer,28 colon cancer,20 breast cancer,29 bladder cancer,30 and liver cancer 31. It has been demonstrated that overexpression of DcR3 was correlated with tumor differentiation, lymph node metastasis, as well as TNM stage and prognosis,32 while downregulation of DcR3 could inhibit the proliferation and migration of tumor cells and increase the apoptosis of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of DcR3 sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis

Liang¹,

Yang²,

Li³

et al. 2017

OTT

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Decoy receptor 3 (DcR3) has been recently described as an antiapoptosis and prometastasis factor since it can competitively bind to FasL, TL1A, and LIGHT, and it is highly expressed in many malignant tumors. Downregulation of DcR3 can promote tumor cell apoptosis and inhibit metastasis. A previous study demonstrated that reduction of DcR3 could induce tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in pancreatic cancer cells. However, whether such an effect is seen in hepatocellular carcinoma (HCC) remains to be explored. This study was designed to investigate the sensitivity of HCC cells to TRAIL after silencing DcR3, and this was done by evaluating the expression of DcR3 in HCC cells and the effect on TRAIL-mediated apoptosis after downregulation of DcR3. Our data showed that DcR3 was highly expressed in HepG2, BEL-7402, Hep3B, Huh-7, MHCC97H, and SMCC7721 cell lines compared with normal liver cell line LO-2. Both HepG2 and BEL-7402 were tolerant to TRAIL-mediated apoptosis, and the tolerance was negatively correlated to the expression of DcR3. Silencing of DcR3 with shRNA and treatment with TRAIL induced obvious apoptosis in HepG2 and BEL-7402, with more cancer cells found in the G1 phase. SiDcR3 combined with TRAIL could induce activation of caspases-3, -8, and -9, raise the expression of the apoptotic protein Bax, and reduce the expression of antiapoptotic proteins (Bcl-2, Mcl-1, Bcl-XL, IAP-2, and survivin). Caspase-8 inhibitor Ac-IETD-CHO significantly decreased the activation of caspase cascade, indicating that the extrinsic pathway may have a vital role in the apoptotic events induced by SiDcR3/TRAIL. Furthermore, our results showed that the TRAIL death receptor 5 (DR5) was upregulated and that DR5 neutralizing antibody abrogated the effect of SiDcR3. Our results demonstrated that downregulation of DcR3 could enhance TRAIL-mediated apoptosis in HCC through the death receptor pathway. In the future, this might be useful as a clinical treatment method of liver cancer.

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Overexpression and Clinicopathological Contribution of DcR3 in Bladder Urothelial Carcinoma Tissues

Cited by 9 publications

References 29 publications

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC

DcR3 induces epithelial-mesenchymal transition through activation of the TGF-β3/SMAD signaling pathway in CRC

The role of the TNF receptors and apoptosis inducing ligands in tumor growth

Downregulation of DcR3 sensitizes hepatocellular carcinoma cells to TRAIL-induced apoptosis

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