CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest

Pan, Wen; Cheng, Yingying; Zhang, Heyu; Liu, Baocai; Mo, Xiaoning; Li, Ting; Li, Lin; Cheng, Xiaoxing; Zhang, Lianhai; Ji, Jiafu; Wang, Pingzhang; Han, Wenling

doi:10.1038/srep06812

Cited by 58 publications

(61 citation statements)

References 61 publications

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“…Based on all the aforementioned analyses, we hypothesized that GPR15 could be a novel target of cancer immunotherapy. Recent studies have shown that the known natural ligands of GPR15 are all agonist [22,23]. We thus put more emphasize on the drug discovery specifically for STAD, to identify potential inhibitors of GPR15.…”

Section: D Structure Modeling Of the Gpr15mentioning

confidence: 99%

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An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15

Wang¹,

Wang²,

Xiong³

et al. 2019

Preprint

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G protein-coupled receptor 15 (GPR15, also known as BOB) is an extensively studied orphan GPCR involving HIV infection, colonic inflammation and smoking-related diseases. Recently, GPR15 was deorphanized and its corresponding natural ligand demonstrated an ability of inhibiting cancer cell growth. However, no study reported the potential role of GPR15 in a pancancer manner. Using large-scale publicly available data from the Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases, we found that GPR15 expression is significantly lower in colon adenocarcinoma (COAD) than in normal tissues. And among 33 cancer types, GPR15 expression is significantly correlated with the prognoses of COAD, neck squamous carcinoma (HNSC), lung adenocarcinoma (LUAD) positively and stomach adenocarcinoma (STAD) negatively. This study also revealed that commonly upregulated gene set in the high GPR15 expression group (stratified via median) of COAD, HNSC, LUAD and STAD are enriched in immune systems, indicating that GPR15 might be considered as a potential target for cancer immunotherapy. Furthermore, we modelled the 3D structure of GPR15 and conducted Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: the structure-based virtual screening. The top 8 hits compounds were screened and then subjected to molecular dynamics (MD) simulation for stability analysis. Our study provided novel insights into the role of GPR15 in a pan-cancer manner and discovered a potential hit compound for GPR15antagonists.

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Section: D Structure Modeling Of the Gpr15mentioning

confidence: 99%

“…deorphanized and its ligand can also bind to SUSD2. The co-expression pattern of GPR15L and SUSD2 can suppress proliferation of several tumoral cell lines via G1 arrest [22][23][24]. This finding indicated that GPR15 may be actively involved in cancer progression.…”

mentioning

confidence: 99%

An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15

Wang¹,

Wang²,

Xiong³

et al. 2019

Preprint

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“…To find novel potential cytokines, we established an immunogenomics-based screening platform, as previously reported (5). Several secreted proteins with important functions have been identified (6)(7)(8), among which is cytokine-like 1 (CYTL1).…”

mentioning

confidence: 99%

Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2

Wang

et al. 2016

The Journal of Immunology

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Cytokine-like 1 (CYTL1) is a novel potential cytokine that was first identified in CD34+ cells derived from bone marrow and cord blood, and it was also found using our immunogenomics strategy. The immunobiological functions of CYTL1 remain largely unknown, and its potential receptor(s) has not been identified. A previous proposed hypothesis suggested that CYTL1 had structural similarities with CCL2 and that CCR2 was a potential receptor of CYTL1. In this study, we verify that CYTL1 possesses chemotactic activity and demonstrate that its functional receptor is CCR2B using a series of experiments performed in HEK293 cells expressing CCR2B or CCR2B-EGFP, including chemotaxis, receptor internalization, and radioactive binding assays. CYTL1 chemoattracts human monocytes but not PBLs, and its chemotactic activity toward monocytes is dependent on the CCR2B-ERK pathway. Furthermore, both human and mouse recombinant CYTL1 protein have chemotactic effects on macrophages from wild-type mice but not from Ccr2−/− mice. Furthermore, the chemotactic activity of CYTL1 is sensitive to pertussis toxin. All of the above data confirm that CCR2B is a functional receptor of CYTL1.

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“…Higher levels of ASCL2 have been linked to worse prognosis3. C10orf99 (also known as CSBF) is down-regulated in colon cancer15.…”

Section: Discussionmentioning

confidence: 99%

Colon cancer subtypes: concordance, effect on survival and selection of the most representative preclinical models

Sztupinszki

Győrffy

2016

Sci Rep

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Multiple gene-expression-based subtypes have been proposed for the molecular subdivision of colon cancer in the last decade. We aimed to cross-validate these classifiers to explore their concordance and their power to predict survival. A gene-chip-based database comprising 2,166 samples from 12 independent datasets was set up. A total of 22 different molecular subtypes were re-trained including the CCHS, CIN25, CMS, ColoGuideEx, ColoGuidePro, CRCassigner, MDA114, Meta163, ODXcolon, Oncodefender, TCA19, and V7RHS classifiers as well as subtypes established by Budinska, Chang, DeSousa, Marisa, Merlos, Popovici, Schetter, Yuen, and Watanabe (first authors). Correlation with survival was assessed by Cox proportional hazards regression for each classifier using relapse-free survival data. The highest efficacy at predicting survival in stage 2–3 patients was achieved by Yuen (p = 3.9e-05, HR = 2.9), Marisa (p = 2.6e-05, HR = 2.6) and Chang (p = 9e-09, HR = 2.35). Finally, 61 colon cancer cell lines from four independent studies were assigned to the closest molecular subtype.

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CSBF/C10orf99, a novel potential cytokine, inhibits colon cancer cell growth through inducing G1 arrest

Cited by 58 publications

References 61 publications

An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15

An Integrated Pan-Cancer Analysis and Structure-Based Virtual Screening of GPR15

Cytokine-like 1 Chemoattracts Monocytes/Macrophages via CCR2

Colon cancer subtypes: concordance, effect on survival and selection of the most representative preclinical models

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