Down-regulation of CXCL 11 inhibits colorectal cancer cell growth and epithelial-mesenchymal transition

Gao, Yu; Liu, De Lin; Li, Sheng; Yuan, Gao; Li, Li; Zhu, Hong; Cao, Gaun Yi

doi:10.2147/ott.s167872

Cited by 40 publications

(32 citation statements)

References 23 publications

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“…This chemokine is overexpressed in colorectal cancer tissues and cell lines, and its downregulation inhibits cell migration and invasion. Moreover, downregulation of CXCL11 has been shown to reduce colorectal cancer cell growth and metastasis in a xenograft model (24). Finally, the present study revealed that CCL4 expression was downregulated by lonidamine, DON and orlistat treatment.…”

Section: Discussionsupporting

confidence: 62%

A combination of inhibitors of glycolysis, glutaminolysis and de�novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

et al. 2019

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Lonidamine, 6-Diazo-5-oxo-L-norleucine (DON) and orlistat are well known inhibitors of glycolysis, glutaminolysis and of de novo fatty acid synthesis, respectively. Although their antitumor effects have been explored in detail, the potential inhibition of the malignant metabolic phenotype and its influence on the expression of chemokines and growth factors involved in colon cancer, have not been previously reported to the best of our knowledge. In the present study, dose-response curves with orlistat, lonidamine or DON were generated from cell viability assays conducted in SW480 colon cancer cells. In addition, the synergistic effect of these compounds was evaluated in SW480 human colon cancer cells. The determination of the doses used for maximum synergistic efficacy led to the exploration of the mRNA levels of the target genes hexokinase-2 (HK2), glutaminase-1 (GLS-1) and fatty acid synthase (FASN) in human SW480 and murine CT26.WT colon cancer cells. The cell viability was evaluated following transfection with small interfering (si)RNA targeting these genes and was assessed with trypan blue. The expression levels of chemokines and growth factors were quantified in the supernatant of SW480 cells with LEGENDplex™. The combination of lonidamine, DON and orlistat resulted in a synergistic cytotoxic effect and induced the transcription of the corresponding gene targets but their corresponding proteins were actually downregulated. The downregulation of the expression levels of HK2, GLS-1 and FASN following transfection of the cells with the corresponding siRNA sequences decreased their viability. The treatment significantly reduced the expression levels of 9 chemokines [interleukin-9, C-X-C motif chemokine ligand (CXCL) 10, eotaxin, chemokine ligand (CCL) 9, CXCL5, CCL20, CXCL1, CXCL11 and CCCL4] and one growth factor (stem cell factor). These changes were associated with decreased phosphorylated-nuclear factor κB-p65. The data demonstrate that lonidamine, DON and orlistat in combination reduce the expression levels of chemokines and growth factors in colon cancer cells. Additional research is required to investigate the exact way by which both tumor and stromal cells regulate the expression levels of chemokines and growth factors.

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Section: Discussionsupporting

confidence: 62%

A combination of inhibitors of glycolysis, glutaminolysis and de�novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

et al. 2019

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“…CXCL11 is overexpressed in CRC tissues and cell lines. Repression of CXCL11 significantly inhibited cell migration, invasion and epithelial-mesenchymal transition (EMT) (37). It was also reported that its downregulation can inhibit tumor angiogenesis in epithelial OV (38).…”

Section: Discussionmentioning

confidence: 96%

Development and Verification of an Immune-Related Gene Pairs Prognostic Signature in Ovarian Cancer

Wang

Bao

Nie

et al. 2020

Preprint

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Background: Ovarian cancer (OV) is the most common gynecological cancer and is a major cause of cancer-related death among women worldwide. Immunotherapy has recently been of great interest, and it has been proven to be an effective treatment strategy. For this reason, the work here attempts to produce a prognostic immune-related gene pair (IRGP) signature to estimate OV patient survival. Methods: The Gene ExpressionOmnibus (GEO) and the Cancer Genome Atlas (TCGA) databases provided the genetic expression profiles and clinical data of OV patients, whose samples were divided into training, validation, and testing sets. The InnateDB database and the least absolute shrinkage and selection operator (LASSO) regression model, were used to build an IRGP signature. The functional enrichment analysis was performed to investigate the biological activities of IRGPs. Then, the correlation between risk scores and clinicopathological parameters was further analyzed. Finally, we compared our signature and four existing signatures for OV. Results: We first identified a 17-IRGP signature significantly associated with survival based on LASSO regression model. The average area under the curve (AUC) values of the training, validation, and all

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“…In this study, we found that patients with high abundance of intratumoral CXCL11 + cells in ltration had better survival and CXCL11 was found to have independent prognostic value in colon cancer. Considering that CXCL11-producing cells were a variety of heterogeneous cells [17] and the intercellular communication mediated by CXCL11 was complicated, the discoveries make sense [26,35].…”

Section: Discussionmentioning

confidence: 99%

CXCL11 Correlates with Anti-tumor Immune Microenvironment and Improved Prognosis in Colon Cancer

Cao

Zhang

Jiao

et al. 2020

Preprint

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Background: CXCL11 has been considered to be responsible for tumor development, but the specific effect of CXCL11 in colon cancer was still obscure. Therefore, the prognostic value and immunological regulation effect of CXCL11 in colon cancer were evaluated in this study.Methods: Three independent datasets were used for mRNA-related analysis: one dataset from the Cancer Genome Atlas (TCGA, n=451) and two single-cell RNA sequencing (scRNA-seq) datasets from Gene Expression Omnibus (GEO): GSE146771 and GSE132465. In addition, the patient cohort (the Yijishan Hospital cohort, YJSHC, n=108) was utilized for cell infiltration-related analysis, accordingly. Both CXCL11 mRNA expression and CXCL11+ (CXCL11-producing) cells were assessed in colon cancer, whose effect on prognosis and immunological regulation was also studied. Results: High CXCL11 expression were associated with better prognosis in colon cancer, which was still significant even if clinicopathological factors were adjusted. Furthermore, CXCL11 positively correlated with anti-tumor cells infiltration, such as CD8+ T cells and natural killer cells. Meanwhile, CXCL11 correlated positively with several genes associated with DC, NK and T recruitment，and a gene set of cytotoxic genes. Notably, CXCL11 correlated positively with several immune checkpoint related genes including of PD-L1. Conclusions: CXCL11 contributed to anti-tumor immune microenvironment and could improve prognosis in patients with colon cancer. Especially, it’s a potential approach that inducible expression of CXCL11 by genetic and pharmacological interventions is able to improve prognosis and response to anti-PD-1 (programmed cell death protein-1) antibody treatment in colon cancer. However, it requires to be verified by further prospective investigations.

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Down-regulation of CXCL 11 inhibits colorectal cancer cell growth and epithelial-mesenchymal transition

Cited by 40 publications

References 23 publications

A combination of inhibitors of glycolysis, glutaminolysis and de�novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

A combination of inhibitors of glycolysis, glutaminolysis and de�novo fatty acid synthesis decrease the expression of chemokines in human colon cancer cells

Development and Verification of an Immune-Related Gene Pairs Prognostic Signature in Ovarian Cancer

CXCL11 Correlates with Anti-tumor Immune Microenvironment and Improved Prognosis in Colon Cancer

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