Detection of collagen triple helix repeat containing-1 and nuclear factor (erythroid-derived 2)-like 3 in colorectal cancer

Palma, Marco; López, Lissette; García, Margarita; Roja, Nuria de la; Ruiz, Tamara; García, Julita; Rosell, Elisabet; Vela, Carmen; Rueda, Paloma; Rodríguez, M J

doi:10.1186/1472-6890-12-2

Cited by 13 publications

(6 citation statements)

References 30 publications

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“…Cthrc1 downregulation may be interpreted as cancer protective, since Cthrc1 is reported to be upregulated in various types of cancer (e.g. ) and its increase is associated with increased motility of lung adenocarcinomas , involving an increase in the planar cell polarity pathway. However, since both Cthrc1 and Fzd6 are downregulated with a similar fold change and p ‐value, the net effect is difficult to predict.…”

Section: Discussionmentioning

confidence: 99%

Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1^−/− mice

Helden

Godschalk

Schooten

et al. 2012

Molecular Nutrition Food Res

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Scope Whole genome transcriptome analysis of male and female beta‐carotene 15,15′‐monooxygenase knockout (Bcmo1−/−) and Bcmo1+/+ (wild‐type) mice with or without 14 wk of BC supplementation was done. We previously showed that only 1.8% of the genes regulated by BC in lung were also regulated in liver and inguinal white adipose tissue (iWAT), suggesting lung specific responses. Here, we explicitly questioned the lung specificity. Methods and results We show that BC supplementation resulted in an opposite direction of gene‐regulation in male compared to female Bcmo1−/− mice in lung, liver, and iWAT. This supports a systemic effect of BC on steroid hormone metabolism mediated responses. Lung, liver, and iWAT of female Bcmo1−/− mice showed an increased inflammatory response, which was counteracted by supplementation of BC. This supports a genotype dependent increased sensitivity of female mice for vitamin A deficiency. Finally, the effect of BC on Wnt signaling in male Bcmo1−/− mice was examined. Frizzled homolog 6 (Fzd6) downregulation was seen in all three tissues. Collagen triple helix containing 1 (Cthrc1) downregulation was seen in lung tissue only, suggesting specificity. Upregulation of genes involved in oxygen sensing was seen in lung and iWAT, while protocadherin upregulation was only seen in lung. Conclusion Our results demonstrate that effects of BC are strongly sex dependent. While effects of BC on hormone metabolism mediated responses and inflammation are systemic, effects on Wnt signaling may be lung specific.

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Section: Discussionmentioning

confidence: 99%

Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1^−/− mice

Helden

Godschalk

Schooten

et al. 2012

Molecular Nutrition Food Res

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“…NFE2L3 , a gene regulating the cell cycle progression in colon cancer [22], was upregulated in CTS with the second highest ES. Interestingly, both CTHRC1 and NFE2L3 have been indicated as useful biomarker candidates for CRC diagnosis because of their overexpression in adenomas and CRC relative to normal tissue [23]. SULF1 , whose expression in tumor stroma is a prognostic marker in advanced pancreatic cancer [24], was upregulated in CTS with the third highest ES.…”

Section: Resultsmentioning

confidence: 99%

Identification of Transcriptional Signatures of Colon Tumor Stroma by a Meta-Analysis

Uddin

Wang

2019

Journal of Oncology

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Background. The tumor stroma plays pivotal roles in influencing tumor growth, invasion, and metastasis. Transcriptional signatures of colon tumor stroma (CTS) are significantly associated with prognosis of colon cancer. Thus, identification of the CTS transcriptional features could be useful for colon cancer diagnosis and therapy. Methods. By a meta-analysis of three CTS gene expression profiles datasets, we identified differentially expressed genes (DEGs) between CTS and colon normal stroma. Furthermore, we identified the pathways, upstream regulators, and protein-protein interaction (PPI) network that were significantly associated with the DEGs. Moreover, we analyzed the enrichment levels of immune signatures in CTS. Finally, we identified CTS-associated gene signatures whose expression was significantly associated with prognosis in colon cancer. Results. We identified numerous significantly upregulated genes (such as CTHRC1, NFE2L3, SULF1, SOX9, ENC1, and CCND1) and significantly downregulated genes (such as MYOT, ASPA, KIAA2022, ARHGEF37, BCL-2, and PPARGC1A) in CTS versus colon normal stroma. Furthermore, we identified significantly upregulated pathways in CTS that were mainly involved in cellular development, immune regulation, and metabolism, as well as significantly downregulated pathways in CTS that were mostly metabolism-related. Moreover, we identified upstream TFs (such as SUZ12, NFE2L2, RUNX1, STAT3, and SOX2), kinases (such as MAPK14, CSNK2A1, CDK1, CDK2, and CDK4), and master metabolic transcriptional regulators (MMTRs) (such as HNF1A, NFKB1, ZBTB7A, GATA2, and GATA5) regulating the DEGs. We found that CD8+ T cells were more enriched in CTS than in colon normal stroma. Interestingly, we found that many of the DEGs and their regulators were prognostic markers for colon cancer, including CEBPB, PPARGC1, STAT3, MTOR, BCL2, JAK2, and CDK1. Conclusions. The identification of CTS-specific transcriptional signatures may provide insights into the tumor microenvironment that mediates the development of colon cancer and has potential clinical implications for colon cancer diagnosis and treatment.

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“…Microarray analyses have identified Cthrc1 as a gene overexpressed in many cancers [2] , [3] [4] [5] , [6] , [7] , [8] , [9] , [10] , [11] , [12] with reports of Cthrc1 localization in cancer cells as determined by immunohistochemistry. It does not appear that the specificity of any commercial antibody was verified using negative control tissues from Cthrc1 null species.…”

Section: Resultsmentioning

confidence: 99%

“…Since our discovery, Cthrc1 has frequently been identified as a gene upregulated in tumors based on microarray-based screening approaches [2] . Among the cancer cells reported to express Cthrc1 are melanomas [2] , [3] , hepatocellular carcinoma [4] , oral cancer [5] , breast ductal carcinoma [6] , [7] , pancreatic cancer [8] , colorectal cancer [9] , [10] , gastric cancer [11] , and dermatofibrosarcoma protuberans [12] . A recent study by Spector et al [13] reported expression of Cthrc1 in myofibroblasts in muscular dystrophies.…”

Section: Introductionmentioning

confidence: 99%

Elevated Plasma Levels of the Pituitary Hormone Cthrc1 in Individuals with Red Hair but Not in Patients with Solid Tumors

et al. 2014

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BackgroundAn increasing number of studies report that Cthrc1 is expressed in various cancer cells. The present study sought to identify which cells in tumors and remodeling tissues express Cthrc1 and investigate the range of circulating human Cthrc1 levels in health and disease.Methodology/Principle FindingsHighly specific monoclonal antibodies were generated to detect Cthrc1 by ELISA in plasma and in tissues by immunohistochemistry. In human colon, gastric, breast, endometrial, pancreatic, kidney, lung and skin cancer, Cthrc1 was expressed by activated stromal cells and not the cancer cells themselves. Similarly, conditions evoking tissue remodeling, such as wound repair or angiotensin II-mediated hypertension, induced Cthrc1 expression in interstitial and adventitial fibroblasts and perivascular stromal cells. Levels of Cthrc1 in plasma from healthy subjects were near the lower detection limit except for individuals with red hair, who had up to several hundred fold higher levels. Elevated Cthrc1 was also found in patients with diabetes, inflammatory conditions, and infections, but not solid tumors. Transgenic mouse studies suggested that Cthrc1 expression by stromal cells does not contribute to circulating levels. In human pituitaries, Cthrc1 was expressed in the anterior and intermediate lobes with unencapsulated Cthrc1 accumulations typically surrounded by chromophobe cells.ConclusionsWe identify Cthrc1 as a marker for activated stromal cells. Cthrc1 is a pituitary hormone with significantly elevated levels in subjects carrying variant alleles of the melanocortin-1 receptor as wells as in patients with inflammatory conditions.

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Detection of collagen triple helix repeat containing-1 and nuclear factor (erythroid-derived 2)-like 3 in colorectal cancer

Cited by 13 publications

References 30 publications

Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1^−/− mice

Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1^−/− mice

Identification of Transcriptional Signatures of Colon Tumor Stroma by a Meta-Analysis

Elevated Plasma Levels of the Pituitary Hormone Cthrc1 in Individuals with Red Hair but Not in Patients with Solid Tumors

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Detection of collagen triple helix repeat containing-1 and nuclear factor (erythroid-derived 2)-like 3 in colorectal cancer

Cited by 13 publications

References 30 publications

Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1−/− mice

Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1−/− mice

Identification of Transcriptional Signatures of Colon Tumor Stroma by a Meta-Analysis

Elevated Plasma Levels of the Pituitary Hormone Cthrc1 in Individuals with Red Hair but Not in Patients with Solid Tumors

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Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1^−/− mice

Organ specificity of beta‐carotene induced lung gene‐expression changes in Bcmo1^−/− mice