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      Integrin αvβ8 serves as a Novel Marker of Poor Prognosis in Colon Carcinoma and Regulates Cell Invasiveness through the Activation of TGF-β1

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          Abstract

          Integrin αvβ8 expressed on tumor cells executes crucial regulatory functions during cell adhesion in the tumor microenvironment and supports the activation of TGF-β1. This study aimed to investigate the expression of integrin αvβ8 and its clinical significance in colon cancer, in addition to its influence on the invasion and migration of cancer cells. Our results showed that integrin αvβ8 was an indicator of progression and poor prognosis in patients with colon cancer. Moreover, integrin αvβ8 significantly promoted the invasion and migration of colon cancer cells by the activation of TGF-β1 and upregulation of metalloproteinase-9. Furthermore, suppression of integrin αvβ8 was found to inhibit the growth of colon cancer in vivo. Our results indicate that integrin αvβ8 promotes tumor invasiveness and the migration of colon cancer through TGF-β1 activation and is a potential prognostic biomarker. This study may provide clues to further understand the manner in which the tumor microenvironment mediates the development of colon cancer and develop strategies for novel therapeutic targets in the prevention and treatment of colon cancer.

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          Most cited references 29

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          Adhesion signaling - crosstalk between integrins, Src and Rho.

          Interactions between cells and the extracellular matrix coordinate signaling pathways that control various aspects of cellular behavior. Integrins sense the physical properties of the extracellular matrix and organize the cytoskeleton accordingly. In turn, this modulates signaling pathways that are triggered by various other transmembrane receptors and augments the cellular response to growth factors. Over the past years, it has become clear that there is extensive crosstalk between integrins, Src-family kinases and Rho-family GTPases at the heart of such adhesion signaling. In this Commentary, we discuss recent advances in our understanding of the dynamic regulation of the molecular connections between these three protein families. We also discuss how this signaling network can regulate a range of cellular processes that are important for normal tissue function and disease, including cell adhesion, spreading, migration and mechanotransduction.
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            An assay for transforming growth factor-beta using cells transfected with a plasminogen activator inhibitor-1 promoter-luciferase construct.

            Transforming growth factor-beta (TGF-beta) is a potent regulator of cellular differentiation, proliferation, migration, and protein expression. These properties have been exploited to create a variety of bioassays for detecting the mature growth factor. In this paper, we describe a highly sensitive and specific, nonradioactive quantitative bioassay for TGF-beta based on its ability to induce plasminogen activator inhibitor-1 (PAI-1) expression. Mink lung epithelial cells (MLEC) were stably transfected with an expression construct containing a truncated PAI-1 promoter fused to the firefly luciferase reporter gene. Addition of TGF-beta (0.2 to > 30 pM) to the transfectants resulted in a dose-dependent increase in luciferase activity in the cell lysates. Although responsive to TGF-beta, this promoter fragment was only minimally influenced by other known inducers of PAI-1 expression. When compared to the widely used MLEC assay, this assay demonstrated greater sensitivity and specificity, allowing quantification of TGF-beta in complex biological solutions.
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              Integrins as biomechanical sensors of the microenvironment

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                Author and article information

                Journal
                J Cancer
                J Cancer
                jca
                Journal of Cancer
                Ivyspring International Publisher (Sydney )
                1837-9664
                2020
                6 April 2020
                : 11
                : 13
                : 3803-3815
                Affiliations
                [1 ]Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China
                [2 ]Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China
                [3 ]Department of Hepatobiliary Surgery, Qilu Hospital, Shandong University, Jinan 250012 Shandong, China
                [4 ]Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 20032, China
                [5 ]Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong, China
                Author notes
                ✉ Corresponding author: Benjia Liang, Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250021, Shandong, China. Tel/Fax: +86 531 68773215; E-mail: liangbj127@ 123456hotmail.com

                Competing Interests: The authors have declared that no competing interest exists.

                Article
                jcav11p3803
                10.7150/jca.43826
                7171496
                © The author(s)

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

                Categories
                Research Paper

                Oncology & Radiotherapy

                integrin αvβ8, colon cancer, prognostic factors, cell invasiveness, tgf-β1

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