Dataset Information

Bioinformatic Analyses and Experimental Verification Reveal that High FSTL3 Expression Promotes EMT via Fibronectin-1/α5β1 Interaction in Colorectal Cancer.

ABSTRACT: Background: Colorectal cancer (CRC) is a typical cancer prevalent worldwide. Despite the conventional treatments, CRC has a poor prognosis due to relapse and metastasis. Moreover, there is a dearth of sensitive biomarkers for predicting prognosis in CRC. Methods: This study used a bioinformatics approach combining validation experiments to examine the value of follistatin-like 3 (FSTL3) as a prognostic predictor and therapeutic target in CRC. Results: FSTL3 was remarkably upregulated in the CRC samples. FSTL3 overexpression was significantly associated with a poor prognosis. FSTL3 was found to activate the epithelial-mesenchymal transition by promoting the binding of FN1 to α5β1. FSTL3 expression was also positively correlated with the abundance of the potent immunosuppressors, M2 macrophages. Conclusion: FSTL3 overexpression affects CRC prognosis and thus, FSTL3 can be a prognostic biomarker and therapeutic target with potential applications in CRC.

SUBMITTER: Liu Y

PROVIDER: S-EPMC8652210 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Bioinformatic Analyses and Experimental Verification Reveal that High FSTL3 Expression Promotes EMT via Fibronectin-1/α5β1 Interaction in Colorectal Cancer.

Liu Yuanjie Y Li Jiepin J Zeng Shuhong S Zhang Ying Y Zhang Yonghua Y Jin Zhichao Z Liu Shenlin S Zou Xi X

Frontiers in molecular biosciences 20211124

Background: Colorectal cancer (CRC) is a typical cancer prevalent worldwide. Despite the conventional treatments, CRC has a poor prognosis due to relapse and metastasis. Moreover, there is a dearth of sensitive biomarkers for predicting prognosis in CRC. Methods: This study used a bioinformatics approach combining validation experiments to examine the value of follistatin-like 3 (FSTL3) as a prognostic predictor and therapeutic target in CRC. Results: FSTL3 was ...[more]

PMID: 34901156

Similar Datasets

Project description:Objective- Alterations in extracellular matrix quantity and composition contribute to atherosclerosis, with remodeling of the subendothelial basement membrane to an FN (fibronectin)-rich matrix preceding lesion development. Endothelial cell interactions with FN prime inflammatory responses to a variety of atherogenic stimuli; however, the mechanisms regulating early atherogenic FN accumulation remain unknown. We previously demonstrated that oxLDL (oxidized low-density lipoprotein) promotes endothelial proinflammatory gene expression by activating the integrin α5β1, a classic mediator of FN fibrillogenesis. Approach and Results- We now show that oxLDL drives robust endothelial FN deposition and inhibiting α5β1 (blocking antibodies, α5 knockout cells) completely inhibits oxLDL-induced FN deposition. Consistent with this, inducible endothelial-specific α5 integrin deletion in ApoE knockout mice significantly reduces atherosclerotic plaque formation, associated with reduced early atherogenic inflammation. Unlike TGFβ (transforming growth factor β)-induced FN deposition, oxLDL does not induce FN expression (mRNA, protein) or the endothelial-to-mesenchymal transition phenotype. In addition, we show that cell-derived and plasma-derived FN differentially affect endothelial function, with only cell-derived FN capable of supporting oxLDL-induced VCAM-1 (vascular cell adhesion molecule 1) expression, despite plasma FN deposition by oxLDL. The inclusion of alternative exon EIIIA (EDA) of FN (EIIIA) and alternative exon EIIIB (EDB) of FN (EIIIB) domains in cell-derived FN mediates this effect, as EIIIA/EIIIB knockout endothelial cells show diminished oxLDL-induced inflammation. Furthermore, our data suggest that EIIIA/EIIIB-positive cellular FN is required for maximal α5β1 recruitment to focal adhesions and FN fibrillogenesis. Conclusions- Taken together, our data demonstrate that endothelial α5 integrins drive oxLDL-induced FN deposition and early atherogenic inflammation. Additionally, we show that α5β1-dependent endothelial FN deposition mediates oxLDL-dependent endothelial inflammation and FN fibrillogenesis.

Dataset Information

Bioinformatic Analyses and Experimental Verification Reveal that High FSTL3 Expression Promotes EMT via Fibronectin-1/α5β1 Interaction in Colorectal Cancer.

Publications

Bioinformatic Analyses and Experimental Verification Reveal that High FSTL3 Expression Promotes EMT <i>via</i> Fibronectin-1/α5β1 Interaction in Colorectal Cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets