SCC-S2 Facilitates Tumor Proliferation and Invasion via Activating Wnt Signaling and Depressing Hippo Signaling in Colorectal Cancer Cells and Predicts Poor Prognosis of Patients

Yang, Chuanjia; Xu, Weixue; Meng, Xiangzhen; Zhou, Siqi; Zhang, Minglu; Cui, Dongxu

doi:10.1369/0022155418799957

Cited by 9 publications

(9 citation statements)

References 30 publications

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“…The results demonstrated that the mRNA levels of TNFAIP8, TIPE1, TIPE2 and TIPE3 in the CRC tissues were significantly lower compared with those in the paired adjacent tissues. Previous studies have demonstrated that the expression of TNFAIP8 protein is upregulated in ~50% of cancer tissues compared with adjacent non-tumor tissue in patients with CRC and is associated with the degree of malignancy of the tumor (34,36). However, it is unclear whether TNFAIP8 isoform a functions in cancer and whether the levels of TNFAIP8 v2 mRNA increases alongside those of TNFAIP8 isoform b in CRC tissues.…”

Section: Discussionmentioning

confidence: 99%

Expression of TIPE family members in human colorectal cancer

et al. 2020

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The tumor necrosis factor α-induced protein 8 (TNFAIP8)-like (TIPE) protein family comprises four members, namely TNFAIP8, TIPE1, TIPE2 and TIPE3, which are involved in multiple processes in cancer. The current study aimed to investigate the expression patterns and potential clinical roles of the TIPE family members in human colorectal cancer (CRC). Paired tumor and adjacent tissue samples were collected from 49 patients with CRC, and the relative mRNA expression levels of the TIPE family members in these samples were evaluated by using reverse transcription-quantitative PCR, and the protein levels in five randomly selected pairs of tumor and adjacent tissue samples were detected by western blot analysis. The mRNA expression levels of the TIPE family members were significantly downregulated in CRC tumor tissues compared with those in the adjacent tissues; however, within each sample, TNFAIP8 and TIPE3 protein levels were only partially consistent with their mRNA levels. In addition, the mRNA expression levels between each pair of TIPE family members exhibited a positive linear relationship, and TIPE2 mRNA levels exhibited strong linear associations with those of TNFAIP8 and TIPE1. TNFAIP8 mRNA expression levels in tumor tissues were significantly associated with the tumor differentiation grade, and TIPE2 mRNA expression levels in tumor tissues were significantly associated with sex. TIPE1 and TIPE3 mRNA expression levels in tumor tissues exhibited no associations with patient clinicopathological characteristics. In addition, the mRNA expression patterns of the TIPE family members were analyzed using data from The Cancer Genome Atlas data set, and the results also demonstrated that TNFAIP8, TIPE2 and TIPE3 mRNA levels were downregulated in patients with colon adenocarcinoma compared with those in normal controls. These results provided evidence that the four members of the TIPE family may affect each other to mediate the carcinogenesis of CRC, and that TIPE2 may serve an important role in CRC.

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Section: Discussionmentioning

confidence: 99%

Expression of TIPE family members in human colorectal cancer

et al. 2020

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“…The Hippo-signaling pathway has been found to be frequently inactivated in multiple human cancer types,9, 10, 11 including CRC 17, 18, 19. Numerous studies have reported that the downregulation of the Hippo pathway components mammalian MST1/2 and LATS1/2 or the upregulation of YAP or TAZ consistently contributed to the inactivation of Hippo signaling, which further promoted the progression of CRC 24, 25, 26.…”

Section: Discussionmentioning

confidence: 99%

“…Several lines of evidence have shown that the inactivation of Hippo signaling was implicated in various processes of CRC. For example, REGγ contributed to the growth of CRC cells via directly interacting with LATS1, leading to the degradation of LATS1 and inactivation of Hippo signaling; 17 in addition, SCC-S2 overexpression was found to promote the invasion and metastasis of CRC via depressing Hippo signaling 18 . Our previous study demonstrated that the inactivation of Hippo signaling by the overexpression of TFAP2C promoted the progression of CRC via maintaining cancer stem cell-like phenotypes 19 .…”

Section: Introductionmentioning

confidence: 92%

ZNF280A Promotes Proliferation and Tumorigenicity via Inactivating the Hippo-Signaling Pathway in Colorectal Cancer

Wang

Sun

Tai

et al. 2019

Molecular Therapy - Oncolytics

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Aberrant expression of zinc-finger proteins has been extensively reported to contribute to malignant progression in a variety of cancers. However, clinical significance and biological roles of ZNF280A in the field of cancer are poorly known. In this study, the expression of ZNF280A was detected in clinical colorectal cancer (CRC) tissues. Functional experiments in vitro and animal experiment in vivo were performed to measure the effect of ZNF280A on the proliferation and tumorigenesis in CRC cells. Western blot and luciferase assays were used to identify the underlying pathway mediating the biological roles of ZNF280A in CRC. Here we report that ZNF280A was upregulated in CRC tissues and cells and a high expression of ZNF280A correlated with tumor, lymph node, and metastasis (TNM) classifications, clinical stage, and predicted poor prognosis and disease progression in CRC patients. Moreover, silencing ZNF280A repressed proliferation and induced G0 and/or G1 arrest in vitro , and it inhibited tumorigenesis of CRC cells in vivo . Our results further demonstrate that silencing ZNF280A inhibited the proliferation of CRC cells by activating Hippo signaling. Therefore, our results uncover a novel mechanistic understanding of ZNF280A-mediated tumor progression in CRC, and meanwhile they provide a novel prognostic factor in CRC patients and a potential therapeutic target for the treatment of CRC.

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“…Yang et al. confirmed that TIPE can promote tumor proliferation and invasion by activating Wnt signaling and inhibiting Hippo signaling in CRC ( 11 ). Our previous studies showed that TIPE was highly expressed in stage III gastric cancer and was positively correlated with DcR3 and ERK1/2 ( 20 ).…”

Section: Discussionmentioning

confidence: 99%

“…TIPE has been reported to be overexpressed in colon cancer and to regulate cell proliferation ( 10 ). The latest research shows that TIPE can promote tumor proliferation and invasion by activating Wnt signaling and inhibiting Hippo signaling in CRC cells ( 11 ). Our previous studies showed that TIPE promotes angiogenesis in CRC by regulating VEGFR2 expression.…”

Section: Introductionmentioning

confidence: 99%

TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC

et al. 2021

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Tumor necrosis factor-induced protein-8 (TIPE) is highly expressed in colorectal cancer (CRC). Decoy receptor 3 (DcR3) is a soluble secreted protein that can antagonize Fas ligand (FasL)-induced apoptosis and promote tumorigenesis. It remains unclear whether TIPE can regulate DcR3 expression. In this study, we examined this question by analyzing the relationship between these factors in CRC. Bioinformatics and tissue microarrays were used to determine the expression of TIPE and DcR3 and their correlation in CRC. The expression of TIPE and DcR3 in colon cancer cells was detected. Plasma samples were collected from CRC patients, and DcR3 secretion was measured. Then, dual-luciferase reporter gene analysis was performed to assess the interaction between TIPE and DcR3. We exogenously altered TIPE expression and analyzed its function and influence on DcR3 secretion. Lipopolysaccharide (LPS) was used to stimulate TIPE-overexpressing HCT116 cells, and alterations in signaling pathways were detected. Additionally, inhibitors were used to confirm molecular mechanisms. We found that TIPE and DcR3 were highly expressed in CRC patients and that their expression levels were positively correlated. DcR3 was highly expressed in the plasma of cancer patients. We confirmed that TIPE and DcR3 were highly expressed in HCT116 cells. TIPE overexpression enhanced the transcriptional activity of the DcR3 promoter. TIPE activated the PI3K/AKT signaling pathway to regulate the expression of DcR3, thereby promoting cell proliferation and migration and inhibiting apoptosis. In summary, TIPE and DcR3 are highly expressed in CRC, and both proteins are associated with poor prognosis. TIPE regulates DcR3 expression by activating the PI3K/AKT signaling pathway in CRC, thus promoting cell proliferation and migration and inhibiting apoptosis. These findings may have clinical significance and promise for applications in the treatment or prognostication of CRC.

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SCC-S2 Facilitates Tumor Proliferation and Invasion via Activating Wnt Signaling and Depressing Hippo Signaling in Colorectal Cancer Cells and Predicts Poor Prognosis of Patients

Cited by 9 publications

References 30 publications

Expression of TIPE family members in human colorectal cancer

Expression of TIPE family members in human colorectal cancer

ZNF280A Promotes Proliferation and Tumorigenicity via Inactivating the Hippo-Signaling Pathway in Colorectal Cancer

TIPE Regulates DcR3 Expression and Function by Activating the PI3K/AKT Signaling Pathway in CRC

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