THBS1 facilitates colorectal liver metastasis through enhancing epithelial–mesenchymal transition

Liu, X; Xu, Da; Liu, Z; Li, Y; Zhang, Cenai; Gong, Yiyi; Jiang, Yang; Xing, Baocai

doi:10.1007/s12094-020-02308-8

Cited by 44 publications

(41 citation statements)

References 36 publications

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“…In addition, survival analysis showed that high THBS1 expression was significantly associated with shorter OS and DFS in GC. The results are consistent with previous studies that THBS1 promotes liver metastasis in colorectal cancer by promoting epithelial-mesenchymal transition, 25 and high expression in cutaneous T-cell lymphoma promotes tumor invasion and metastasis, leading to poor prognosis. 7 The above suggests that THBS1 is associated with poor prognosis in GC.…”

Section: Discussionsupporting

confidence: 93%

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Zhang¹,

Huang²,

Li³

et al. 2021

IJGM

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Purpose Thrombospondin 1 ( THBS1 ) is an endogenous inhibitor of angiogenesis, but it also promotes tumor invasion, metastasis, and immune response in the tumor environment. Previous research has found that THBS1 is highly expressed in many tumors and has a negative correlation with tumor prognosis. However, research on the relationship between THBS1 and immune infiltration in GC is less well documented, and the objective of our study was to investigate the role of THBS1 expression in GC. Patients and Methods The expression of THBS1 in GC was analyzed by Oncomine, TIMER, TGCA, GEO and IHC staining. Analysis of the signaling pathways associated with THBS1 expression in GC uses GSEA. The relationship between THBS1 expression and immune infiltration was analyzed by the ESTIMATE algorithm, single-cell transcriptome analysis, TIMER2 database and CIBERSORT algorithm. Finally, the relationship between THBS1 expression and drug sensitivity was analyzed by the CellMiner database. Results THBS1 was overexpressed in GC and was associated with poor prognosis, and high THBS1 expression was an independent risk factor. GSEA results showed that high THBS1 expression in GC was associated with tumorigenesis, adhesion, and significant immune enrichment. THBS1 expression was most strongly correlated with tumor-associated macrophages (TAMs), M2 macrophages and cancer-associated fibroblast (CAFs) in GC. THBS1 expression positively correlates with most immune checkpoint members, suggesting that THBS1 may play an important role in the tumor microenvironment. THBS1 overexpression was negatively correlated with some drug sensitivities, such as Oxaliplatin. Conclusion Upregulation of THBS1 was positively correlated with poor prognosis and immunosuppression in GC and negatively correlated with anticancer drug sensitivity, suggesting that THBS1 may serve as a potential target for the treatment of GC.

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Section: Discussionsupporting

confidence: 93%

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Zhang¹,

Huang²,

Li³

et al. 2021

IJGM

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“…Many of the ten key mRNAsi-related genes we screened have been reported in CRC, and some of them have also received attention in the CSCs eld. For instance, CRC patients with high VCAN expression have a poor prognosis (20), which is consistent with the results of our study. Recent reports have shown that the proliferation, invasion, and migration of colon cancer cells are promoted by inhibinting subunit beta A through up-regulation of VCAN (21).…”

Section: Discussionsupporting

confidence: 93%

Identification of Hub Genes for Controlling Cancer Stem Cell Characteristics in Colorectal Cancer by Bioinformatics Analysis

Li¹,

Huang²,

Zheng³

2021

Preprint

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Background Cancer stem cells (CSCs), which are capable of infinite proliferation and self-renewal, play a crucial role in the occurrence and development of colorectal cancer (CRC). The study of the expression characteristics of CRC stem cell-related genes and their interaction with the immune microenvironment may contribute to CRC treatment. Results In order to explore the hub genes that regulate the stemness characteristics of CRC, we obtained gene expression values of the Cancer Genome Atlas (TCGA), stemness indices (mRNAsi), and corresponding survival data from UCSC Xena Browser. Differentially expressed genes (DEGs) were identified in cancer and normal tissues. Then we screened 2 modules and 210 mRNAsi-related genes from 4,941 DEGs by weighted gene co-expression network analysis. A prognostic model including ten genes (VCAN, SPARC, COL12A1, THBS2, COL1A2, COL5A1, TAGLN, DCN, MYH11, CDH11) was constructed using protein interaction networks and LASSO regression. We also evaluated the relationship between cancer stemness and immune response and found there was a strong correlation between each other. Conclusions Our study establishes a prognostic model associated with CSCs and reveals the association between mRNAsi and the tumor immune microenvironment, which is useful for the targeted therapy of CRC.

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“…Some studies suggest that THBS1 to be a biomarker for monitoring a primary myelofibrosis targeted therapy (37). Moreover, THBS1 is a secreted protein that acts in the tumor microenvironment to inhibit angiogenesis, regulate antitumor immunity, tumor cell migration, and influence the activities of extracellular proteases and growth factor, which plays an important role in tumor progression (18,40). In our study, we also found that the levels of THBS1 in advance stage were significantly higher than normal samples in TCGA breast invasive carcinoma database.…”

Section: Discussionmentioning

confidence: 99%

“…The above experimental data confirmed that tRF-17-79MP9PP could inhibit breast malignant activities of cancer cells, so its target gene should be associated with tumor cell invasion, metastasis or proliferation. Based on the rationale, four candidate genes (THBS1, KIF3A, RAB10, RFX5) were selected after a literature review (18)(19)(20)(21)(22)(23). Further analysis revealed that tRF-17-79MP9PP had "seed sequences", which may bind to the 3'UTR of the four candidate genes according to TargetScan and miRanda programs (Figure 4B).…”

Section: Go and Kegg Enrichment Analysis Of Trf-17-79mp9pp Target Genesmentioning

confidence: 99%

tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer

Zheng

et al. 2021

Front. Oncol.

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tRNA derivatives have been identified as a new kind of potential biomarker for cancer. Previous studies have identified that there were 30 differentially expressed tRNAs derivatives in breast cancer tissue with the high-throughput sequencing technique. This study aimed to investigate the possible biological function and mechanism of tRNA derivatives in breast cancer cells. One such tRF, a 5’-tRF fragment of tRF-17-79MP9PP (tRF-17) was screened in this study, which is processed from the mature tRNA-Val-AAC and tRNA-Val-CAC. tRF-17 with significantly low expression in breast cancer tissues and serum. The level of tRF-17 differentiated breast cancer from healthy controls with sensitivity of 70.4% and specificity of 68.4%. Overexpression of tRF-17 suppressed cells malignant activity. THBS1 (Thrombospondin-1) as a downstream target of tRF-17, and reduction of THBS1 expression also partially recovered the effects of tRF-17 inhibition on breast cancer cell viability, invasion and migration. Besides, THBS1, TGF-β1, Smad3, p-Smad3 and epithelial-to-mesenchymal transition related genes N-cadherin, MMP3, MMP9 were markedly down-regulated in tRF-17 overexpressing cells. Moreover, tRF-17 attenuated the THBS1-mediated TGF-β1/Smad3 signaling pathway in breast cancer cells. In general, the tRF-17/THBS1/TGF-β1/smad3 axis elucidates the molecular mechanism of breast cancer cells invasion and migration and could lead to a potential therapeutic target for breast cancer.

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THBS1 facilitates colorectal liver metastasis through enhancing epithelial–mesenchymal transition

Cited by 44 publications

References 36 publications

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Upregulation of THBS1 is Related to Immunity and Chemotherapy Resistance in Gastric Cancer

Identification of Hub Genes for Controlling Cancer Stem Cell Characteristics in Colorectal Cancer by Bioinformatics Analysis

tRNA-Derived Fragment tRF-17-79MP9PP Attenuates Cell Invasion and Migration via THBS1/TGF-β1/Smad3 Axis in Breast Cancer

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