<i>C8orf4</i> is a transforming growth factor B induced transcript downregulated in metastatic colon cancer

Friedman, Joshua B.; Brunschwig, Elaine; Platzer, Petra; Wilson, Keith E.; Markowitz, Sanford D.

doi:10.1002/ijc.20235

Cited by 29 publications

(23 citation statements)

References 16 publications

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“…It is present only in vertebrates and encodes a protein of 106 amino acids without identified functional domain (2,3). It has been implicated in cancer and signal transduction (4,5). However, the clinical relevance and precise biological functions have not heretofore been elucidated.…”

Section: Introductionmentioning

confidence: 99%

TC1 (C8orf4) Enhances the Wnt/β-Catenin Pathway by Relieving Antagonistic Activity of Chibby

Jung¹,

Bang²,

Choi³

et al. 2006

Cancer Research

104

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The Wnt/B-catenin pathway has been implicated in human cancers. Here, we show that TC1 (C8orf4), a small protein present in vertebrates, functions as a positive regulator of the pathway. TC1 interacts with Chibby (Cby) and thereby enhances the signaling pathway by relieving the antagonistic function of Cby on the B-catenin-mediated transcription. Upon coexpression in mammalian cells, TC1 redistributes from nucleolus to nuclear speckles, where it colocalizes with Cby. TC1 upregulates the expression of B-catenin target genes that are implicated in invasiveness and aggressive behavior of cancers, such as metalloproteinases, laminin ;2, and others. Our data indicate that TC1 is a novel upstream regulator of the Wnt/Bcatenin pathway that enhances aggressive behavior of cancers. (Cancer Res 2006; 66(2): 723-8)

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Section: Introductionmentioning

confidence: 99%

TC1 (C8orf4) Enhances the Wnt/β-Catenin Pathway by Relieving Antagonistic Activity of Chibby

Jung¹,

Bang²,

Choi³

et al. 2006

Cancer Research

104

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“…TC1(C8orf4) is a novel gene up-regulated in certain cancers (5)(6)(7)(8)(9). It is associated with metastasis and poor survival (9).…”

mentioning

confidence: 99%

TC1(C8orf4) Is a Novel Endothelial Inflammatory Regulator Enhancing NF-κB Activity

Kim¹,

Kim²,

Kim

et al. 2009

The Journal of Immunology

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Endothelial inflammation is regulated by a complex molecular mechanism. TC1(C8orf4) is a novel regulator implicated in cancer and inflammation. It is a small protein conserved well among vertebrates. In zebrafish embryos, it is mostly expressed in angio-hematopoietic system and the overexpression induces edema. In human aortic endothelial cells and umbilical vein endothelial cells, TC1 transfection up-regulates key inflammatory cytokines, enzymes, and adhesion proteins including IL-6, IL-1α, COX-2, CXCL1, CCL5, CCL2, IL-8, ICAM1, VCAM1, and E-selectin, while TC1 knockdown down-regulates them. TC1 also enhances inflammatory parameters such as monocyte-endothelial adhesion and endothelial monolayer permeability. TC1 is up-regulated by IL-1β, TNF-α, LPS, and phorbol ester, and the up-regulation is inhibited by I-κB-kinase inhibitors. TC1, in turn, enhances the nuclear translocation of RelA and the DNA binding activity, suggesting a biological role of amplifying NF-κB signaling via a positive feedback. Our findings suggest that TC1 is a novel endothelial inflammatory regulator that might be implicated in inflammatory vascular diseases.

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“…It is present in vertebrates and encodes a protein of 106 amino acids without an identified functional domain (7,8). It has been implicated in cancer and signal transduction (9,10). However, its clinical relevance and precise biological functions have not heretofore been elucidated.…”

mentioning

confidence: 99%

TC1(C8orf4) Correlates with Wnt/β-Catenin Target Genes and Aggressive Biological Behavior in Gastric Cancer

Kim

Koo²,

Yang

et al. 2006

Clinical Cancer Research

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Purpose: We have recently reported that TC1(C8orf4), a small protein present in vertebrates, functions as a novel regulator of the Wnt/h-catenin pathway. TC1 up-regulates h-catenin target genes that are implicated in the aggressive behavior of cancers. Our aim was to investigate the clinical and pathobiological relevance of TC1in gastric cancer. Experimental Design: The expression of TC1 was analyzed using tissue microarray in correlation with clinicopathologic variables and h-catenin target genes in 299 gastric cancers. The biological effects of TC1on Matrigel invasiveness and the proliferation of cancer cells were analyzed. TC1 expression was analyzed in gastric cancer cells after serial peritoneal implantation in nude mice. Results: TC1 expression was present in 111 carcinomas (37.1%), correlating with tumor stage (P < 0.002), poor differentiation (P < 0.001), lymphatic infiltration (P < 0.005), and lymph node metastasis (P < 0.006). TC1 also correlated with poor survival in diffuse type carcinomas (P < 0.0001), and even in patients with lymph node metastasis (P < 0.0014). TC1also correlated with the expression of h-catenin target genes including laminin g2, metalloproteinase-7 and metalloproteinase-14, cyclin D1, c-Met, and CD44. TC1 enhanced Matrigel invasiveness and proliferation, supporting its role in the aggressive biological behavior of cancers. The expression of TC1increased in MKN45 cells after serial peritoneal seeding in nude mice. Conclusions: Our data suggests thatTC1coordinates the up-regulation of Wnt/h-catenin target genes that are implicated in the aggressive biological behavior of cancers. The strong clinical relevance, even in patients with lymph node metastasis, suggested that TC1could be a potential therapeutic target of advanced gastric cancers.

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C8orf4 is a transforming growth factor B induced transcript downregulated in metastatic colon cancer

Cited by 29 publications

References 16 publications

TC1 (C8orf4) Enhances the Wnt/β-Catenin Pathway by Relieving Antagonistic Activity of Chibby

TC1 (C8orf4) Enhances the Wnt/β-Catenin Pathway by Relieving Antagonistic Activity of Chibby

TC1(C8orf4) Is a Novel Endothelial Inflammatory Regulator Enhancing NF-κB Activity

TC1(C8orf4) Correlates with Wnt/β-Catenin Target Genes and Aggressive Biological Behavior in Gastric Cancer

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