Vimentin filament controls integrin α5β1‐mediated cell adhesion by binding to integrin through its Ser38 residue

Kim, Jiyoon; Jang, Jungim; Yang, Chansik; Kim, Eun Jin; Jung, Hosung; Kim, Chungho

doi:10.1002/1873-3468.12430

Cited by 22 publications

(24 citation statements)

References 25 publications

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“…Importantly, endogenous FN expression in tumor cells has been found to be promoted by upregulation of vimentin during E-M plastic processes [281,282], suggesting again that elevated endogenous FN expression in metastatic CTCs results in better periFN assembly to sustain stability of microtentacles, which not only protect CTCs from mechanical stresses existing in the circulation but also pave ways for CTCs to colonize distant organs. This conclusion is well supported by the findings that vimentin inhibition with withaferin A abolishes binding of FN to integrin α5β1, one of cell surface receptors mediating periFN assembly [283]. Further supporting evidence is that the ability of vimentin in controlling integrin recycling depends on the phosphorylation mediated by PKCε [284], which has been revealed to promote periFN assembly on blood-borne breast cancer cells and lung metastasis [265].…”

Section: Fn Expression In Ctcs Facilitates Distant Organ Colonizationmentioning

confidence: 71%

Fibronectin in Cancer: Friend or Foe

Lin

Yang

et al. 2019

Cells

147

117

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The role of fibronectin (FN) in tumorigenesis and malignant progression has been highly controversial. Cancerous FN plays a tumor-suppressive role, whereas it is pro-metastatic and associated with poor prognosis. Interestingly, FN matrix deposited in the tumor microenvironments (TMEs) promotes tumor progression but is paradoxically related to a better prognosis. Here, we justify how FN impacts tumor transformation and subsequently metastatic progression. Next, we try to reconcile and rationalize the seemingly conflicting roles of FN in cancer and TMEs. Finally, we propose future perspectives for potential FN-based therapeutic strategies. Figure 1. (A) The structure of fibronectin (FN) containing three types of repeats and three alternative splicing regions (EDA, EDB, and IIICS) with several well-known binding sites for extracellular matrix (ECM) components (fibrin, heparin, collagen, and gelatin), polymeric assembly (FN-FN), cell adhesion (integrin α5β1), DPP IV, and two C-terminal disulfide bonds for dimeric FN. (B) Publications in recent some forty years regarding the roles of cancerous FN and stromal FN in ECM in tumor progression as represented in a time-line pattern. Among 26 publications before 2000, 15 (57.7%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 3 (11.5%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 8 (30.8%) papers are related to the role of stromal FN in promoting early tumor progression but not late metastasis (in dark green boxes). On the contrary, Among 46 publications after 2000, 7 (15.2%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 25 (54.4%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 14 (30.4%) papers are related to the role of stromal FN in promoting early tumor progression but not late metastasis (in dark green boxes). Abbreviations in boxes are referred to the context of this article. (C) Percentages of articles for the three various roles of FN (the same colors as depicted in (B) before 2000 and after 2000. Numbers in the parenthesis represent article numbers. The Pathobiology of CancerFigure 1. (A) The structure of fibronectin (FN) containing three types of repeats and three alternative splicing regions (EDA, EDB, and IIICS) with several well-known binding sites for extracellular matrix (ECM) components (fibrin, heparin, collagen, and gelatin), polymeric assembly (FN-FN), cell adhesion (integrin α5β1), DPP IV, and two C-terminal disulfide bonds for dimeric FN. (B) Publications in recent some forty years regarding the roles of cancerous FN and stromal FN in ECM in tumor progression as represented in a time-line pattern. Among 26 publications before 2000, 15 (57.7%) papers are related to the role of cancerous FN in tumor suppression (in light green boxes), 3 (11.5%) papers are related to the role of cancerous FN in metastasis promotion (in orange boxes), and 8 (30.8%) papers are related to the r...

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Section: Fn Expression In Ctcs Facilitates Distant Organ Colonizationmentioning

confidence: 71%

Fibronectin in Cancer: Friend or Foe

Lin

Yang

et al. 2019

Cells

147

117

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“…Adhesion molecules play an important role for the stability of the tissue structure but also for adherence of circulating cells to the endothelial lining as a first step of transmigration through the endothelial barrier. Changes in the expression of cadherins but also of vimentin controlling integrin function [21] may therefore affect the ability of cell adherence. For this reason, the stability of cell binding to an artificial surface and the development of a stable cellular layer was measured under acidic conditions.…”

Section: Resultsmentioning

confidence: 99%

Extracellular Acidosis Modulates the Expression of Epithelial-Mesenchymal Transition (EMT) Markers and Adhesion of Epithelial and Tumor Cells

et al. 2019

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Epithelial-to-mesenchymal transition (EMT) is an important process of tumor progression associated with increased metastatic potential. EMT can be activated by external triggers such as cytokines or metabolic parameters (e.g. hypoxia). Since extracellular acidosis is a common finding in tumors, the aim of the study is to analyze its impact on the expression of EMT markers in vitro and in vivo as well as the functional impact on cell adhesion. Therefore, three tumor and two normal epithelial cell lines were incubated for 24 h at pH 6.6 and the expression of EMT markers was studied. In addition, mRNA expression of transcription and metabolic factors related to EMT was measured as well as the functional impact on cell adhesion, either during acidic incubation or after priming cells in an acidic milieu. E-cadherin and N-cadherin were down-regulated in all tumor and normal cell lines studied, whereas vimentin expression increased in only two tumor and one normal cell line. Down-regulation of the cadherins was seen in total protein and to a lesser extent in surface protein. In vivo an increase in N-cadherin and vimentin expression was found. Acidosis up-regulated Twist1 and Acsl1 but down-regulated fumarate hydratase (Fh). Cell adhesion during acidic incubation decreased in AT1 prostate carcinoma cells whereas preceding acidic priming increased their subsequent adhesion. Low tumor pH is able to modulate the expression EMT-related proteins and by this may affect the stability of the tissue structure.

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“…Consistent with our finding that NEDD9-bound vimentin is not phosphorylated at Ser56, WFA was reported to inhibit breast cancer cell invasion and metastasis by inducing Ser56 phosphorylation and vimentin disassembly [61] . Ser38 is another site of regulatory phosphorylation which has been shown to increase vimentin binding to α5β1 integrin [62] . In this context, inhibition of vimentin phosphorylation by pkCε inhibited endocytiosis of integrin-containing vesicles and cell haptotaxis [63] .…”

Section: Discussionmentioning

confidence: 99%

Vimentin and Non-Muscle Myosin IIA are Members of the Neural Precursor Cell Expressed Developmentally Down-Regulated 9 (NEDD9) Interactome in Head and Neck Squamous Cell Carcinoma Cells

Šemeláková¹,

Grauzam

Betadthunga³

et al. 2019

Translational Oncology

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Here we demonstrate an interaction between neural precursor cell expressed, developmentally-downregulated 9 (NEDD9) and the cytoskeletal proteins vimentin and non-muscle myosin IIA (NMIIA), based on co-immunoprecipitation and mass spectrometric sequence identification. Vimentin was constitutively phosphorylated at Ser56 but vimentin associated with NEDD9-was not phosphorylated at Ser56. In contrast, NMIIA bound to NEDD9 was phosphorylated on S1943 consistent with its function in invasion and secretion. Treatment of cells with the vimentin-targeting steroidal lactone withaferin A had no effect on vimentin turnover as previously reported, instead causing NEDD9 cleavage and cell death. The NMIIA-selective inhibitor blebbistatin induced cells to form long extensions and attenuated secretion of matrix metalloproteinases (MMPs) 2 and 9. While the site of vimentin interaction on NEDD9 was not defined, NMIIA was found to interact with NEDD9 at its substrate domain. NEDD9 interactions with vimentin and NMIIA are consistent with these proteins having roles in MMP secretion and cell invasion. These findings suggest that a better understanding of NEDD9 signaling is likely to reveal novel therapeutic targets for the prevention of invasion and metastasis.

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Vimentin filament controls integrin α5β1‐mediated cell adhesion by binding to integrin through its Ser38 residue

Cited by 22 publications

References 25 publications

Fibronectin in Cancer: Friend or Foe

Fibronectin in Cancer: Friend or Foe

Extracellular Acidosis Modulates the Expression of Epithelial-Mesenchymal Transition (EMT) Markers and Adhesion of Epithelial and Tumor Cells

Vimentin and Non-Muscle Myosin IIA are Members of the Neural Precursor Cell Expressed Developmentally Down-Regulated 9 (NEDD9) Interactome in Head and Neck Squamous Cell Carcinoma Cells

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