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      Fluid shear stress induces cell migration and invasion via activating autophagy in HepG2 cells

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          ABSTRACT

          Fluid shear stress (FSS) regulates the metastasis of hepatocellular carcinoma (HCC). In the present study, we aimed to study the role of autophagy in HCC cells under FSS. The results showed that FSS upregulated the protein markers of autophagy, induced LC3B aggregation and formation of autophagosomes. Inhibition of integrin by Cliengitide (Cli) or inhibition of the microfilaments formation both inhibited the activation of autophagy in HepG2 under FSS. In addition, Cli inhibited the microfilaments formation and expressions of Rac1 and RhoA in HepG2 cells under FSS. Finally, inhibition of autophagy suppressed the cell migration and invasion in HepG2 under FSS. In conclusion, FSS induced autophagy to promote migration and invasion of HepG2 cells via integrin/cytoskeleton pathways.

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          Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE Study

          Joong-Won Park, Minshan Chen, Massimo Colombo … (2015)
          Background & Aims Hepatocellular carcinoma (HCC) is the second most common cause of cancer deaths worldwide. The global HCC BRIDGE study was a multiregional, large-scale, longitudinal cohort study undertaken to improve understanding of real-life management of patients with HCC, from diagnosis to death. Methods Data were collected retrospectively from January 2005 to September 2012 by chart reviews of eligible patients newly diagnosed with HCC at participating institutions. Results Forty-two sites in 14 countries contributed final data for 18 031 patients. Asia accounted for 67% of patients, Europe for 20% and North America for 13%. As expected, the most common risk factor was hepatitis C virus in North America, Europe and Japan, and hepatitis B virus in China, South Korea and Taiwan. The most common Barcelona Clinic Liver Cancer stage at diagnosis was C in North America, Europe, China and South Korea, and A in Taiwan and Japan. Across all stages, first HCC treatment was most frequently transarterial chemoembolization in North America, Europe, China and South Korea, percutaneous ethanol injection or radiofrequency ablation in Japan and resection in Taiwan. Survival from first HCC treatment varied significantly by region, with median overall survival not reached for Taiwan and 60, 33, 31, 24 and 23 months for Japan, North America, South Korea, Europe and China respectively (P < 0.0001). Conclusions Initial results from the BRIDGE study confirm previously reported regional trends in patient demographic characteristics and HCC risk factors, document the heterogeneity of treatment approaches across regions/countries and underscore the need for earlier HCC diagnosis worldwide.
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            Activation of integrins in endothelial cells by fluid shear stress mediates Rho-dependent cytoskeletal alignment.

            E Tzima, José Pozo, Jana Schwartz … (2001)
            Fluid shear stress is a critical determinant of vascular remodeling and atherogenesis. Both integrins and the small GTPase Rho are implicated in endothelial cell responses to shear but the mechanisms are poorly understood. We now show that shear stress rapidly stimulates conformational activation of integrin alpha(v)beta3 in bovine aortic endothelial cells, followed by an increase in its binding to extracellular cell matrix (ECM) proteins. The shear-induced new integrin binding to ECM induces a transient inactivation of Rho similar to that seen when suspended cells are plated on ECM proteins. This transient inhibition is necessary for cytoskeletal alignment in the direction of flow. The results therefore define the role of integrins and Rho in a pathway leading to endothelial cell adaptation to flow.
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              Functions of autophagy in the tumor microenvironment and cancer metastasis

              Marina N. Sharifi, Erin E Mowers, Kay F Macleod (2018)
              Macro-autophagy is an ancient and highly-conserved self-degradative process that plays a homeostatic role in normal cells by eliminating organelles, pathogens and protein aggregates. Autophagy, as it is routinely referred to, also allows cells to maintain metabolic sufficiency and survive under conditions of nutrient stress by recycling the by-products of autophagic degradation, such as fatty acids, amino acids and nucleotides. Tumor cells are more reliant than normal cells on autophagy for survival in part due to their rapid growth rate, altered metabolism and nutrient deprived growth environment. How this dependence of tumor cells on autophagy affects their progression to malignancy and metastatic disease is an area of increasing research focus. Here, we review recent work identifying critical functions for autophagy in tumor cell migration and invasion, tumor stem cell maintenance and therapy resistance and cross-talk between tumor cells and their microenvironment. Autophagy is upregulated as tumors progress to become malignant and this review addresses how autophagy modulates cancer metastasis. Specifically, we examine the critical role played by autophagy in tumor cell migration and invasion, in maintaining the cancer stem cell phenotype and tumor cell dormancy as well as how autophagy affects interactions of tumor cells with components of the tumor microenvironment. Finally, we discuss how these functions make autophagy inhibition an attractive therapeutic option for metastatic cancers.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Cell Adh Migr
                Journal ID (iso-abbrev): Cell Adh Migr
                Journal ID (publisher-id): KCAM
                Journal ID (publisher-id): kcam20
                Title: Cell Adhesion & Migration
                Publisher: Taylor & Francis
                ISSN (Print): 1933-6918
                ISSN (Electronic): 1933-6926
                Publication date Collection: 2019
                Publication date (Electronic): 31 January 2019
                Publication date PMC-release: 31 January 2019
                Volume: 13
                Issue: 1
                Pages: 152-163
                Affiliations
                Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University , Chengdu, China
                Author notes
                CONTACT Ye Zeng ye@ 123456scu.edu.cn
                Xiaoheng Liu liuxiaohg@ 123456scu.edu.cn Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University , No.17, Section 3, Renmin South Road, Chengdu, Sichuan 610041, P.R. China
                Article
                Publisher ID: 1568141
                DOI: 10.1080/19336918.2019.1568141
                PMC ID: 6550537
                PubMed ID: 30663937
                SO-VID: db07d70f-92b8-4810-be67-62ea9d93d75f
                Copyright © © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 31 October 2018
                Date revision received : 12 December 2018
                Date accepted : 2 January 2019
                Page count
                Figures: 7, References: 36, Pages: 12
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: No. 31670960
                This study was supported by National Natural Science Foundation of China (No. 31670960).
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Cell biology
                Keywords: fluid shear stress,autophagy,integrin,cytoskeleton,metastasis
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: fluid shear stress, autophagy, integrin, cytoskeleton, metastasis

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