Dataset Information

Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Cell Invasion through Integrin ?6 Upregulation in Colorectal Cancer.

ABSTRACT: The metastatic potential of colorectal cancer (CRC) is intensively promoted by the tumor microenvironment (TME) in a paracrine manner. As a pleiotropic inflammatory cytokine, Interleukin-6 (IL-6) is produced and involved in CRC, the same scenario where integrin ?v?6 also becomes upregulated. However, the relationship between IL-6 and integrin ?v?6 as well as their involvement in the crosstalk between CRC and TME remains largely unclear. In the present study, we demonstrated a positive correlation between the expression of IL-6 and integrin ?6 in CRC samples. The mutually promotive interaction between CRC and TME was further determined by an indirect coculture system. CRC cells could augment the secretion of IL-6 from fibroblasts, which in return induced invasion and integrin ?6 expression of CRC cells. Through the classic IL-6 receptor/STAT-3 signaling pathway, IL-6 mediated the upregulation of integrin ?6, which was involved in the invasion and epithelial-mesenchymal transition of CRC cells induced by IL-6. Taken together, our results reveal a paracrine crosstalk between IL-6 signals originating from the TME and increased the integrin ?6 level of CRC. IL-6 induces CRC invasion via upregulation of integrin ?6 through the IL-6 receptor/STAT-3 signaling pathway. Combined inhibition of IL-6 along with integrin ?6-targeted strategy may indicate new directions for antitumor strategies for CRC.

SUBMITTER: Sun Q

PROVIDER: S-EPMC7443035 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Cell Invasion through Integrin β6 Upregulation in Colorectal Cancer.

Sun Qi Q Shang Yukui Y Sun Fengkai F Dong Xiwen X Niu Jun J Li Fanni F

Oxidative medicine and cellular longevity 20200813

The metastatic potential of colorectal cancer (CRC) is intensively promoted by the tumor microenvironment (TME) in a paracrine manner. As a pleiotropic inflammatory cytokine, Interleukin-6 (IL-6) is produced and involved in CRC, the same scenario where integrin αvβ6 also becomes upregulated. However, the relationship between IL-6 and integrin αvβ6 as well as their involvement in the crosstalk between CRC and TME remains largely unclear. In the present study, we demons ...[more]

PMID: 32855767

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Project description:BackgroundColorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms.MethodsReal-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-β/Smad signaling pathway-related proteins was investigated using western blotting.ResultsIn this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-βR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-β / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels.ConclusionThe protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-β/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.

Dataset Information

Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Cell Invasion through Integrin ?6 Upregulation in Colorectal Cancer.

Publications

Interleukin-6 Promotes Epithelial-Mesenchymal Transition and Cell Invasion through Integrin <i>β</i>6 Upregulation in Colorectal Cancer.

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