&lt;p&gt;Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer&lt;/p&gt;

Lin, Yan; He, Ziqin; Ye, Jiazhou; Liu, Ziyu; She, Xiaomin; Gao, Xing; Liang, Rong

doi:10.2147/ott.s278013

Cited by 85 publications

(81 citation statements)

References 89 publications

(113 reference statements)

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“…To validate the above findings, we selected the COL1A1 and IL-6 for further study and detected whether they were co-expression in glioma tissues. IL-6, as an important immunosuppressive and immunosuppressive cell recruitment factors, has a profound effect on immune cell infiltration in the tumor immune microenvironment [ 28 , 29 ]. The double-immunofluorescence staining revealed that the co-expression of COL1A1 with IL-6 was found in WHO II-IV grade glioma tissues (Additional file 6 : Fig.…”

Section: Resultsmentioning

confidence: 99%

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

Zhu²,

Tan

et al. 2021

Cancer Cell Int

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Background Gliomas account for the majority of fatal primary brain tumors, and there is much room for research in the underlying pathogenesis, the multistep progression of glioma, and how to improve survival. In our study, we aimed to identify potential biomarkers or therapeutic targets of glioma and study the mechanism underlying the tumor progression. Methods We downloaded the microarray datasets (GSE43378 and GSE7696) from the Gene Expression Omnibus (GEO) database. Then, we used weighted gene co-expression network analysis (WGCNA) to screen potential biomarkers or therapeutic targets related to the tumor progression. ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data) algorithm and TIMER (Tumor Immune Estimation Resource) database were used to analyze the correlation between the selected genes and the tumor microenvironment. Real-time reverse transcription polymerase chain reaction was used to measure the selected gene. Transwell and wound healing assays were used to measure the cell migration and invasion capacity. Western blotting was used to test the expression of epithelial-mesenchymal transition (EMT) related markers. Results We identified specific module genes that were positively correlated with the WHO grade but negatively correlated with OS of glioma. Importantly, we identified that 6 collagen genes (COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2) could regulate the immunosuppressive microenvironment of glioma. Moreover, we found that these collagen genes were significantly involved in the EMT process of glioma. Finally, taking COL3A1 as a further research object, the results showed that knockdown of COL3A1 significantly inhibited the migration, invasion, and EMT process of SHG44 and A172 cells. Conclusions In summary, our study demonstrated that collagen genes play an important role in regulating the immunosuppressive microenvironment and EMT process of glioma and could serve as potential therapeutic targets for glioma management.

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Section: Resultsmentioning

confidence: 99%

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

Zhu²,

Tan

et al. 2021

Cancer Cell Int

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“…IL-6 expression induces CRC invasion via the upregulation of integrin β 6 through the IL-6 receptor/STAT-3 signaling [ 103 ]. Several clinical studies have been conducted targeting the IL-6 pathway in CRC; however, no significant anticancer effects have been observed yet with IL-6 monoclonal antibodies alone [ 104 , 105 , 106 , 107 ].…”

Section: Caf–tumor Communicationmentioning

confidence: 99%

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

Asif

Longobardi

Hahne

et al. 2021

Cancers

126

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Cancer-associated fibroblasts (CAFs) play a key role in cancer progression by contributing to extracellular matrix (ECM) deposition and remodeling, extensive crosstalk with cancer cells, epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and therapy resistance. As metastasis is a main reason for cancer-related deaths, it is crucial to understand the role of CAFs in this process. Colorectal cancer (CRC) is a heterogeneous disease and lethality is especially common in a subtype of CRC with high stromal infiltration. A key component of stroma is cancer-associated fibroblasts (CAFs). To provide new perspectives for research on CAFs and CAF-targeted therapeutics, especially in CRC, we discuss the mechanisms, crosstalk, and functions involved in CAF-mediated cancer invasion, metastasis, and protection. This summary can serve as a framework for future studies elucidating these roles of CAFs.

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“…Several types of therapeutics are available, such as anti-IL-6 or anti-IL-6R antibodies, soluble gp130Fc (sgp130Fc), and selective small-molecule JAK inhibitors, that are used in the treatment of human diseases [ 38 , 74 ]. An IL-6 inhibitor, siltuximab, has been studied in a phase II and III clinical trial (NCT00841191); no clinical activity was observed when the drug was used as a monotherapy, but it was well-tolerated [ 75 ].…”

Section: Clinical Studies On Drugs Targeting Il-6 Signaling For Crc Therapymentioning

confidence: 99%

A Potential Role of IL-6/IL-6R in the Development and Management of Colon Cancer

et al. 2021

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Colorectal cancer (CRC) is the third most frequent cancer worldwide and the second greatest cause of cancer deaths. About 75% of all CRCs are sporadic cancers and arise following somatic mutations, while about 10% are hereditary cancers caused by germline mutations in specific genes. Several factors, such as growth factors, cytokines, and genetic or epigenetic alterations in specific oncogenes or tumor-suppressor genes, play a role during the adenoma–carcinoma sequence. Recent studies have reported an increase in interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels in the sera of patients affected by colon cancer that correlate with the tumor size, suggesting a potential role for IL-6 in colon cancer progression. IL-6 is a pleiotropic cytokine showing both pro- and anti-inflammatory roles. Two different types of IL-6 signaling are known. Classic IL-6 signaling involves the binding of IL-6 to its membrane receptor on the surfaces of target cells; alternatively, IL-6 binds to sIL-6R in a process called IL-6 trans-signaling. The activation of IL-6 trans-signaling by metalloproteinases has been described during colon cancer progression and metastasis, involving a shift from membrane-bound interleukin-6 receptor (IL-6R) expression on the tumor cell surface toward the release of soluble IL-6R. In this review, we aim to shed light on the role of IL-6 signaling pathway alterations in sporadic colorectal cancer and the development of familial polyposis syndrome. Furthermore, we evaluate the possible roles of IL-6 and IL-6R as biomarkers useful in disease follow-up and as potential targets for therapy, such as monoclonal antibodies against IL-6 or IL-6R, or a food-based approach against IL-6.

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<p>Progress in Understanding the IL-6/STAT3 Pathway in Colorectal Cancer</p>

Cited by 85 publications

References 89 publications

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

Identification of collagen genes related to immune infiltration and epithelial-mesenchymal transition in glioma

The Role of Cancer-Associated Fibroblasts in Cancer Invasion and Metastasis

A Potential Role of IL-6/IL-6R in the Development and Management of Colon Cancer

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