Dro1/Ccdc80 inactivation promotes AOM/DSS-induced colorectal carcinogenesis and aggravates colitis by DSS in mice

Grill, Jessica I.; Neumann, Jens; Ofner, Andrea; Marschall, Maximilian K.; Zierahn, Heike; Herbst, Andreas; Wolf, Eckhard; Kolligs, Frank T.

doi:10.1093/carcin/bgy077

Cited by 13 publications

(13 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the present study, we performed transcriptome sequencing to explore the transcriptome changes in CRC cells after NP treatment. We found that the coiled-coil domain containing 80 (CCDC80), a tumor suppressor in CRC, was significantly reduced after NP exposure (Grill et al, 2018). The results of the current study reveal the underlying mechanism of NP exposure in CRC progression and provide novel insights into CRC occurrence and progression.…”

Section: Introductionmentioning

confidence: 68%

Coiled-Coil Domain Containing 80 Suppresses Nonylphenol-Induced Colorectal Cancer Cell Proliferation by Inhibiting the Activation of ERK1/2

Wang

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Recently, the effect of endocrine-disrupting chemicals on the cancer procession has been a concern. Nonylphenol (NP) is a common environmental estrogen that has been shown to enhance the proliferation of colorectal cancer (CRC) cells in our previous studies; however, the underlying mechanism remains unclear. In this study, we confirmed the increased concentration of NP in the serum of patients with CRC. RNA sequencing was used to explore the differentially expressed genes after NP exposure. We found 16 upregulated genes and 12 downregulated genes in COLO205 cells after NP treatment. Among these differentially expressed genes, we found that coiled-coil domain containing 80 (CCDC80) was downregulated by NP treatment and was associated with CRC progression. Further experiments revealed that the overexpression of CCDC80 significantly suppressed NP-induced cell proliferation and recovered the reduced cell apoptosis. Meanwhile, the overexpression of CCDC80 significantly inhibited the activation of ERK1/2 induced by NP treatment. ERK1/2 inhibitor (PD98059) treatment also suppressed NP-induced CRC cell growth, but the overexpression of CCDC80 did not enhance the effect of ERK1/2 inhibitor. Taken together, NP treatment significantly inhibited the expression of CCDC80, and the overexpression of CCDC80 suppressed NP-induced CRC cell growth by inhibiting the activation of ERK1/2. These results suggest that NP could induce CRC cell growth by influencing the expression of multiple genes. CCDC80 and ERK1/2 inhibitors may be suitable therapeutic targets in NP-related CRC progression.

show abstract

Section: Introductionmentioning

confidence: 68%

Coiled-Coil Domain Containing 80 Suppresses Nonylphenol-Induced Colorectal Cancer Cell Proliferation by Inhibiting the Activation of ERK1/2

Wang

Zhang

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

show abstract

“…CCDC80 has been considered as a multipurpose molecule in vertebrates, mediating diverse developmental processes [23]. Using transcriptional profiling, previous publications have identified that CCDC80 may play a role in tumor inhibition, such as ovarian cancer [24], malignant melanoma [25], thyroid [26] and colorectal carcinoma [27]. CCDC80 is expressed in several types of cells, in particular in preadipocytes and adipocytes, while it is temporarily down-regulated during cell differentiation [16].…”

Section: Discussionmentioning

confidence: 99%

A novel association of CCDC80 with gestational diabetes mellitus in pregnant women: a propensity score analysis from a case-control study

Liu

Wang

et al. 2020

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

Background: Gestational diabetes mellitus (GDM) is a growing global epidemic. Our study aims to confirm the association between circulatory coiled-coil domain-containing 80 (CCDC80) in pregnant women with GDM, to investigate the discriminatory power of CCDC80 on GDM, and to explore the relationships between this molecular level and clinical cardiometabolic parameters. Methods: A 1:2 matched case-control study with 61 GDM patients and 122 controls was conducted using a propensity score matching protocol. All participants were screened from a multicenter prospective pre-birth cohort: Born in Shenyang Cohort Study (BISCS). During 24 and 28 weeks of gestation, follow-up individuals underwent an oral glucose tolerance test (OGTT) and blood sampling for cardiometabolic characterization. Results: Following propensity score matching adjustment for clinical variables, including maternal age, gestational age, body mass index, SBP and DBP, plasma CCDC80 levels were significantly decreased in patients with GDM when compared with controls (0.25 ± 0.10 vs. 0.31 ± 0.12 ng/ml, P = 0.003). Conditional multi-logistic regression analyses after adjustments for potential confounding factors revealed that CCDC80 was a strong and independent protective factor for GDM (ORs < 1). In addition, the results of the ROC analysis indicated the CCDC80 exhibited the capability to identify pregnant women with GDM (AUC = 0.633). Finally, multivariate regression analyses showed that CCDC80 levels were positively associated with AST, monoamine oxidase, complement C1q, LDL-C, apolipoprotein A1and B, and negatively associated with blood glucose levels at 1 h post-OGTT. Conclusions: Biomarker CCDC80 could be of great value for the development of prediction, diagnosis and therapeutic strategies against GDM in pregnant women.

show abstract

“…In Apc Min/+ mice ubiquitous inactivation of Dro1/Ccdc80 results in early death, a significant increase in the colonic tumor load, and the regular formation of adenocarcinoma in the colon [ 1 ]. Loss of DRO1/CCDC80 increases multiplicity of preneoplastic aberrant crypt foci and colonic tumors in carcinogen-induced colon carcinogenesis and promotes formation of colon adenocarcinoma during inflammation-driven carcinogenesis [ 6 ]. In colon tumors from Apc Min/+ mice loss of DRO1/CCDC80 induces ERK1/2 phosphorylation and leads to c-MYC oncogene activation [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…To date, the tumor suppressor role of Dro1/Ccdc80 in vivo has always been addressed by ubiquitous gene inactivation in mice [ 1 , 3 , 6 ]. For the study of tumorigenesis this approach implicates Dro1/Ccdc80 deficiency in both the tumor parenchyma and the tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Loss of DRO1/CCDC80 in the tumor microenvironment promotes carcinogenesis

et al. 2022

Self Cite

View full text Add to dashboard Cite

Tumors are composed of the tumor cells and the surrounding microenvironment. Both are closely interwoven and interact by a complex and multifaceted cross-talk which plays an integral part in tumor initiation, growth, and progression. Dro1/ Ccdc80 has been shown to be a potent suppressor of colorectal cancer and ubiquitous inactivation of Dro1/Ccdc80 strongly promoted colorectal carcinogenesis in Apc Min/+ mice and in a chemically-induced colorectal cancer model. The aim of the present study was to investigate whether Dro1/Ccdc80's tumor suppressive function is tumor-cell-autonomous. Expression of Dro1/Ccdc80 in cancer cells had no effect on both colon tumor development in Apc Min/+ mice and formation of xenograft tumors. In contrast, DRO1/CCDC80 loss in the microenvironment strongly increased tumor growth in xenograft models, inhibited cancer cell apoptosis, and promoted intestinal epithelial cell migration. Moreover, stromal Dro1/Ccdc80 inactivation facilitated formation of intestinal epithelial organoids. Expression analyses showed Dro1/Ccdc80 to be significantly down-regulated in murine gastric cancer associated fibroblasts, in Apc Min/+ colon tumor primary stromal cells and in microdissected stroma from human colorectal cancer compared to normal, non-tumor stroma. Our results demonstrate epithelial derived DRO1/CCDC80 to be dispensable for intestinal tissue homeostasis and identify Dro1/Ccdc80 as tumor suppressor in the tumor microenvironment.

show abstract

Dro1/Ccdc80 inactivation promotes AOM/DSS-induced colorectal carcinogenesis and aggravates colitis by DSS in mice

Cited by 13 publications

References 35 publications

Coiled-Coil Domain Containing 80 Suppresses Nonylphenol-Induced Colorectal Cancer Cell Proliferation by Inhibiting the Activation of ERK1/2

Coiled-Coil Domain Containing 80 Suppresses Nonylphenol-Induced Colorectal Cancer Cell Proliferation by Inhibiting the Activation of ERK1/2

A novel association of CCDC80 with gestational diabetes mellitus in pregnant women: a propensity score analysis from a case-control study

Loss of DRO1/CCDC80 in the tumor microenvironment promotes carcinogenesis

Contact Info

Product

Resources

About