Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

Taylor, Gregory A.; Jeffers, Mike; Webb, Craig P.; Koo, Han Mo; Anver, Miriam R.; Sekiguchi, Kiyotoshi; Woude, George F. Vande

doi:10.1038/sj.onc.1202004

Cited by 16 publications

(12 citation statements)

References 14 publications

(21 reference statements)

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“…Recent studies using human mesangial cells have also demonstrated that HGF can suppress TGF-β1 expression induced by a high concentration of glucose [14]. HGF also represses TGF-β1 production [25,26]. Thus, in our study, it seems that HGF alters TGF-β1 regulation at multiple levels.…”

Section: Discussionsupporting

confidence: 69%

Hepatocyte Growth Factor Suppresses Transforming Growth Factor‐Beta‐1 and Type III Collagen in Human Primary Renal Fibroblasts

Mou

Wang

Shi

et al. 2009

The Kaohsiung J of Med Scie

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Tubulointerstitial changes in the diabetic kidney correlate closely with renal fibrosis, and transforming growth factor-beta-1 (TGF-beta1) is thought to play a key role in this process. In contrast, hepatocyte growth factor (HGF) has shown therapeutic effects on injured renal tubules in animal models. This study was undertaken to test the hypothesis that the preventive effects of HGF may result from interventions in TGF-beta1-mediated signaling and collagen III secretion. We examined the expression of HGF/HGF receptor (c-Met) and TGF-beta1 in renal fibroblasts at multiple time points. The effects of recombinant human HGF on TGF-beta1 expression were studied by RT-PCR and Western blotting, and the levels of collagen III were measured by ELISA. In the high-glucose condition, the expression of HGF and c-Met in renal fibroblasts was detected as early as 6 hours following cell culture while the level of TGF-beta1 peaked at 96 hours. The addition of recombinant human HGF to the culture media dose-dependently inhibited TGF-beta1 mRNA expression and reduced collagen III secretion by 34%. These results indicate that, during hyperglycemia, HGF inhibits TGF-beta1 signaling and type III collagen activation in interstitial fibroblasts. Furthermore, we should recognize that changes in the balance between HGF and TGF-beta1 might be decisive in the pathogenesis of chronic renal fibrosis. Therefore, administration of HGF to restore this balance may offer a novel therapeutic intervention in managing renal fibrogenesis in diabetic nephropathy.

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Section: Discussionsupporting

confidence: 69%

Hepatocyte Growth Factor Suppresses Transforming Growth Factor‐Beta‐1 and Type III Collagen in Human Primary Renal Fibroblasts

Mou

Wang

Shi

et al. 2009

The Kaohsiung J of Med Scie

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“…DAB2 is of particular interest since it suppresses signaling from the growth factor signal transduction pathway to AP-1 (33,104) and is down regulated in a variety of human tumors (11,23). Other known tumor suppressor genes, those for thrombospondin 1 (63,78), RECK (69,81,99), TIMP1 (77), IGSF4 (25), gremlin/ CKTSF1B1 (10), sFRP1 (49,98), IGFBP7/MAC25 (96), fibronectin 1 (52,73,101), STAT1 (38), and FAT (21), and some purported tumor suppressor genes, those for brush-1/WASF3 (87), TES (102), and WNT5A (39), are all down-regulated in Tif-Fos cells. The number of tumor suppressor genes that are down-regulated in Tif-Fos cells and their breadth of activities (ECM components, transcription regulators, signal transducers, and protease inhibitors) reflect the complexity of the invasion program and the many aspects of cell biology that are engaged during invasion.…”

Section: Discussionmentioning

confidence: 99%

Invasion of Normal Human Fibroblasts Induced by v-FosIs Independent of Proliferation, Immortalization, and the Tumor Suppressors p16^INK4a and p53

Scott

Vass

Parkinson

et al. 2004

Molecular and Cellular Biology

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Invasion is generally perceived to be a late event during the progression of human cancer, but to date there are no consistent reports of alterations specifically associated with malignant conversion. We provide evidence that the v-Fos oncogene induces changes in gene expression that render noninvasive normal human diploid fibroblasts highly invasive, without inducing changes in growth factor requirements or anchorage dependence for proliferation. Furthermore, v-Fos-stimulated invasion is independent of the pRb/p16INK4a and p53 tumor suppressor pathways and telomerase. We have performed microarray analysis using Affymetrix GeneChips, and the gene expression profile of v-Fos transformed cells supports its role in the regulation of invasion, independent from proliferation. We also demonstrate that invasion, but not proliferation, is dependent on the activity of the up-regulated epidermal growth factor receptor. Taken together, these results indicate that AP-1-directed invasion could precede deregulated proliferation during tumorigenesis and that sustained activation of AP-1 could be the epigenetic event required for conversion of a benign tumor into a malignant one, thereby explaining why many malignant human tumors present without an obvious premalignant hyperproliferative dysplastic lesion.

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“…However, the role of FN in tumorigenesis and malignant progression has been highly controversial [7,8]. On the one hand, it has been reported that FN expression in tumor cells plays a tumor suppressive role to prevent tumor transformation and to halt their early progression [9]. On the other hand, abundant evidence reveals that FN provokes late stages of cancer metastasis and is associated with poor prognosis when endogenously expressed in tumor cells.…”

Section: Introductionmentioning

confidence: 99%

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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Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

Cited by 16 publications

References 14 publications

Hepatocyte Growth Factor Suppresses Transforming Growth Factor‐Beta‐1 and Type III Collagen in Human Primary Renal Fibroblasts

Hepatocyte Growth Factor Suppresses Transforming Growth Factor‐Beta‐1 and Type III Collagen in Human Primary Renal Fibroblasts

Invasion of Normal Human Fibroblasts Induced by v-FosIs Independent of Proliferation, Immortalization, and the Tumor Suppressors p16^INK4a and p53

Fibronectin in Cancer: Friend or Foe

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Decreased fibronectin expression in Met/HGF-mediated tumorigenesis

Cited by 16 publications

References 14 publications

Hepatocyte Growth Factor Suppresses Transforming Growth Factor‐Beta‐1 and Type III Collagen in Human Primary Renal Fibroblasts

Hepatocyte Growth Factor Suppresses Transforming Growth Factor‐Beta‐1 and Type III Collagen in Human Primary Renal Fibroblasts

Invasion of Normal Human Fibroblasts Induced by v-FosIs Independent of Proliferation, Immortalization, and the Tumor Suppressors p16INK4a and p53

Fibronectin in Cancer: Friend or Foe

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Invasion of Normal Human Fibroblasts Induced by v-FosIs Independent of Proliferation, Immortalization, and the Tumor Suppressors p16^INK4a and p53