CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling

Ng, Lui; Wong, Sunny Kit-Man; Huang, Zheng; Chow, Albert H.L.; Foo, Chi Chung; Lo, Oswens Siu-Hung; Pang, Roberta; Law, Wai‐Lun

doi:10.3390/ijms23031181

Cited by 25 publications

(11 citation statements)

References 28 publications

(37 reference statements)

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“…Previous studies indicate that KIF2C promotes the growth, invasion, and metastasis of HCC by mediating the Ras/MAPK signaling pathway (56). MMP1, which is an interstitial collagenase, has been implicated in the proliferation and metastasis in a variety of malignancies (57)(58)(59). HAVCR1 also known as T-cell immunoglobulin mucin domains (TIM)-1, is overexpressed in renal cell carcinoma (60), human colorectal cancer (61), and gastric adenocarcinomas (62), promoting the occurrence and progression of tumors.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Zhu

Zhu²,

Chen³

et al. 2022

Front. Oncol.

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BackgroundLiver cancer is among the leading causes of death related to cancer around the world. The most frequent type of human liver cancer is hepatocellular carcinoma (HCC). Fatty acid (FA) metabolism is an emerging hallmark that plays a promoting role in numerous malignancies. This study aimed to discover a FA metabolism-related risk signature and formulate a better model for HCC patients’ prognosis prediction.MethodsWe collected mRNA expression data and clinical parameters of patients with HCC using the TCGA databases, and the differential FA metabolism-related genes were explored. To create a risk prognostic model, we carried out the consensus clustering as well as univariate and multivariate Cox regression analyses. 16 genes were used to establish a prognostic model, which was then validated in the ICGC dataset. The accuracy of the model was performed using receiver operating characteristic (ROC) analyses, decision curve analysis (DCA) and nomogram. The immune cell infiltration level of risk genes was evaluated with single-sample GSEA (ssGSEA) algorithm. To reflect the response to immunotherapy, immunophenoscore (IPS) was obtained from TCGA-LIHC. Then, the expression of the candidate risk genes (p < 0.05) was validated by qRT-PCR, Western blotting and single-cell transcriptomics. Cellular function assays were performed to revealed the biological function of HAVCR1.ResultsAccording to the TCGA-LIHC cohort analysis, the majority of the FA metabolism-related genes were expressed differentially in the HCC and normal tissues. The prognosis of patients with high-risk scores was observed to be worse. Multivariate COX regression analysis confirmed that the model can be employed as an independent prognosis factor for HCC patients. Furthermore, ssGSEA analysis revealed a link between the model and the levels of immune cell infiltration. Our model scoring mechanism also provides a high predictive value in HCC patients receiving anti-PDL1 immunotherapy. One of the FA metabolism-related genes, HAVCR1, displays a significant differential expression between normal and HCC cell lines. Hepatocellular carcinoma cells (Huh7, and HepG2) proliferation, motility, and invasion were all remarkably inhibited by HAVCR1 siRNA.ConclusionOur study identified a novel FA metabolism-related prognostic model, revealing a better potential treatment and prevention strategy for HCC.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Zhu

Zhu²,

Chen³

et al. 2022

Front. Oncol.

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“…The CD26 inhibitor class of medications has established safety [ 74 ]. Several completed preclinical studies and clinical trials have evaluated the safety and efficacy of CD26 inhibitors in immune-mediated diseases and anti-tumor immune response [ 3 , 65 , 70 ]. Neither severe hypoglycemic events nor serious side effects were observed.…”

Section: Discussionmentioning

confidence: 99%

“…Ng et al also reported that CD26 is an attractive therapeutic target for combating tumor progression to improve the prognosis of CRC patients. The CD26 function in inducing CRC migration, invasion, angiogenesis and metastasis, and the potential involvement of matrix metalloproteinases1 (MMP1) and caveolae (CAV1) in such process were also identified [ 70 ].…”

Section: Cd26 Inhibitors In Anti-tumor Immune Responsementioning

confidence: 99%

Therapeutic Perspectives of CD26 Inhibitors in Imune-Mediated Diseases

Wang

Xue

2022

Molecules

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The enzymatic activity of CD26/DPP4 (dipeptidyl peptidase 4/DPP4) is highlighted in multiple studies to play a vital role in glucose metabolism by cleaving and inactivating the incretins glucagon-like peptide-1 (GLP) and gastric inhibitory protein (GIP). A large number of studies demonstrate that CD26 also plays an integral role in the immune system, particularly in T cell activation. CD26 is extensively expressed in immune cells, such as T cells, B cells, NK cells, dendritic cells, and macrophages. The enzymatic activity of CD26 cleaves and regulates numerous chomokines and cytokines. CD26 inhibitors have been widely used for the treatment of diabetes mellitus, while it is still under investigation as a therapy for immune-mediated diseases. In addition, CD26’s involvement in cancer immunology was also described. The review aims to summarize the therapeutic effects of CD26 inhibitors on immune-mediated diseases, as well as the mechanisms that underpin them.

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“… 54 MMP1 is involved in the induction of CRC migration, invasion, angiogenesis, and metastasis. 55 MMP1 stimulates VEGFR2 expression and endothelial cell proliferation by stimulating PAR-1 and activating NF-κB. 56 A recent study showed that MMP1 downregulation is strongly linked to shorter disease-free periods.…”

Section: Discussionmentioning

confidence: 99%

Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis

Qin

Lin

et al. 2022

Cancer Control

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Objectives This study aimed to investigate the differentiation state and clinical significance of colorectal cancer cells, as well as to predict the immune response and prognosis of patients based on differentiation-related genes of colorectal cancer. Introduction Colorectal cancer cells exhibit different differentiation states under the influence of the tumor microenvironment, which determines the cell fates. Methods We combined single-cell sequencing (scRNA-seq) data from The Cancer Genome Atlas source with extensive transcriptome data from the Gene Expression Omnibus database. We obtained colorectal cancer differentiation-related genes using cell trajectory analysis and developed a colorectal cancer differentiation-related gene based molecular typing and prognostic model to predict the immune response and prognosis of patients with colorectal cancer. Results We identified 5 distinct cell differentiation subsets and 620 colorectal cancer differentiation-related genes. Colorectal cancer differentiation-related genes were significantly associated with metabolism, angiogenesis, and immunity. We separated patients into 3 subtypes based on colorectal cancer differentiation-related gene expression in the tumor and found differences among the different subtypes in immune infiltration status, immune checkpoint gene expression, clinicopathological features, and overall survival. Immunotherapeutic interventions involving a highly expressed immune checkpoint blockade may be selectively effective in the corresponding cancer subtypes. We built a risk score prediction model (5-year AUC: .729) consisting of the 4 most important predictors of survival (TIMP1, MMP1, LGALS4, and ITLN1). Finally, we generated and validated a nomogram consisting of the risk score and clinicopathological variables. Conclusion This study highlights the significance of genes involved in cell differentiation for clinical prognosis and immunotherapy in patients and provides prospective therapeutic targets for colorectal cancer.

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CD26 Induces Colorectal Cancer Angiogenesis and Metastasis through CAV1/MMP1 Signaling

Cited by 25 publications

References 28 publications

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Bioinformatics analysis and experimental verification of the prognostic and biological significance mediated by fatty acid metabolism related genes for hepatocellular carcinoma

Therapeutic Perspectives of CD26 Inhibitors in Imune-Mediated Diseases

Colorectal Cancer Cell Differentiation Trajectory Predicts Patient Immunotherapy Response and Prognosis

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