scholarly journals Matrix stiffness-mediated effects on stemness characteristics occurring in HCC cells

Oncotarget ◽  
2016 ◽  
Vol 7 (22) ◽  
pp. 32221-32231 ◽  
Author(s):  
Yang You ◽  
Qiongdan Zheng ◽  
Yinying Dong ◽  
Xiaoying Xie ◽  
Yaohui Wang ◽  
...  
Keyword(s):  
Matrix Stiffness ◽  
Mediated Effects ◽  
Hcc Cells

scholarly journals Higher matrix stiffness as an independent initiator triggers epithelial-mesenchymal transition and facilitates HCC metastasis

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yinying Dong ◽  
Qiongdan Zheng ◽  
Zhiming Wang ◽  
Xiahui Lin ◽  
Yang You ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Epithelial Mesenchymal Transition ◽  
Liver Stiffness ◽  
Pathological Process ◽  
Matrix Stiffness ◽  
Invasion And Metastasis ◽  
Snail Expression ◽  
Mesenchymal Transition ◽  
Hcc Cells

Abstract Background Increased liver stiffness exerts a detrimental role in driving hepatocellular carcinoma (HCC) malignancy and progression, and indicates a high risk of unfavorable outcomes. However, it remains largely unknown how liver matrix stiffness as an independent cue triggers epithelial-mesenchymal transition (EMT) and facilitates HCC metastasis. Methods Buffalo rat HCC models with different liver stiffness backgrounds and an in vitro Col I-coated cell culture system with tunable stiffness were used in the study to explore the effects of matrix stiffness on EMT occurrence and its underlying molecular mechanism. Clinical significance of liver stiffness and key molecules required for stiffness-induced EMT were validated in HCC cohorts with different liver stiffness. Results HCC xenografts grown in higher stiffness liver exhibited worse malignant phenotypes and higher lung metastasis rate, suggesting that higher liver stiffness promotes HCC invasion and metastasis. Cell tests in vitro showed that higher matrix stiffness was able to strikingly strengthen malignant phenotypes and independently induce EMT occurrence in HCC cells, and three signaling pathways converging on Snail expression participated in stiffness-mediated effect on EMT including integrin-mediated S100A11 membrane translocation, eIF4E phosphorylation, and TGF β1 autocrine. Additionally, the key molecules required for stiffness-induced EMT were highly expressed in tumor tissues of HCC patients with higher liver stiffness and correlated with poor tumor differentiation and higher recurrence. Conclusions Higher matrix stiffness as an initiator triggers epithelial-mesenchymal transition (EMT) in HCC cells independently, and three signaling pathways converging on Snail expression contribute to this pathological process. This work highlights a significant role of biomechanical signal in triggering EMT and facilitating HCC invasion and metastasis.

Matrix stiffness‐mediated effects on macrophages polarization and their LOXL2 expression

FEBS Journal ◽  
2020 ◽  
Author(s):  
Xiaoxia Xing ◽  
Yaohui Wang ◽  
Xi Zhang ◽  
Xiangyu Gao ◽  
Miao Li ◽  
...  
Keyword(s):  
Matrix Stiffness ◽  
Mediated Effects ◽  
Macrophages Polarization

scholarly journals Phosphorylation of the PDH complex precedes HIF-1-mediated effects and PDK1 upregulation during the first hours of hypoxic treatment in HCC cells

Hypoxia ◽  
2016 ◽  
Vol Volume 4 ◽  
pp. 135-145 ◽  
Author(s):  
Claude Haan ◽  
Geoffroy Walbrecq ◽  
Ines Kozar ◽  
Iris Behrmann ◽  
Andreas David Zimmer
Keyword(s):  
Mediated Effects ◽  
Hypoxic Treatment ◽  
Hcc Cells

scholarly journals Matrix stiffness modulates hepatic stellate cell activation into tumor-promoting myofibroblasts via E2F3-dependent signaling and regulates malignant progression

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Zhikui Liu ◽  
Huanye Mo ◽  
Runkun Liu ◽  
Yongshen Niu ◽  
Tianxiang Chen ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Tumor Cells ◽  
Cell Activation ◽  
Stellate Cell ◽  
Smooth Muscle Actin ◽  
Erk Signaling ◽  
Mechanical Stimuli ◽  
Matrix Stiffness ◽  
Hcc Cells

AbstractThe hepatic stellate cells (HSCs) activation by myofibroblastic differentiation is critical for liver fibrosis. Crosstalk between stromal cells and tumor cells in the microenvironment alters the properties and facilitates the growth and metastasis of tumor cells. How mechanical stimuli originally stiffness of extracellular matrix (ECM) contribute to tumor development remains poorly understood. Here, we demonstrated that stiffness contributes to mechanosignal transduction in HSCs, which promotes hepatocellular carcinoma (HCC) cells growth and metastasis through secretion of FGF2. On stiffness matrix, HSCs activation was confirmed by immunofluorescence (IF) and Western blot (WB) for α-smooth muscle actin (SMA). Increasing matrix stiffness promoted HSCs activation by CD36-AKT-E2F3 mechanosignaling through shRNA-mediated E2F3 knockdown, AKT inhibitors, and CD36 shRNA. Moreover, ChIP-qPCR. Confirmed that E2F3 combined the promoter of FGF2, and stiffness promoted FGF2 expression. On a stiff matrix, HCC cells cultured with conditioned media (CM) from HSCs increased HCC cells growth and metastasis by binding FGFR1 to activate PI3K/AKT and MEK/ERK signaling pathways. Moreover, conditional E2F3 knockout mice were subjected to CCl4 treatment to assess the role of E2F3 in HSC activation. Additionally, the DEN-induced HCC model was also used to evaluate the role of E2F3 in liver fibrosis and HCC growth. In conclusion, we demonstrated that stiffness-induced HSC activation by E2F3 dependent. Stiffness activated CD36-AKT-E2F3 signaling and targeted FGF2 transcription, subsequently, activated HCC growth and metastasis by FGFR1-mediated PI3K/AKT and MEK/ERK signaling.

scholarly journals Long noncoding RNA MACC1-AS1 promotes the stemness of hepatocellular carcinoma cells by antagonizing miR-145

2020 ◽  
Vol 48 (4) ◽  
pp. 030006052092041
Author(s):  
Yuling Guo ◽  
Jiuhong Zhong ◽  
Fang Wu ◽  
Zhengyu Zhan
Keyword(s):  
Hepatocellular Carcinoma ◽  
Antisense Rna ◽  
Noncoding Rna ◽  
Carcinoma Cells ◽  
Luciferase Reporter ◽  
Spheroid Formation ◽  
Master Regulators ◽  
Real Time Quantitative Pcr ◽  
Mediated Effects ◽  
Hcc Cells

Objectives This work aimed to investigate the roles of long noncoding (lnc)RNA MACC1-AS1 (MACC1 antisense RNA 1) in progression of hepatocellular carcinoma (HCC). Methods Real-time quantitative PCR, western blot, spheroid formation, aldehyde dehydrogenase isoform 1 (ALDH1) activity analysis, luciferase reporter assay, and RNA pull-down analysis were used to examine MACC1-AS1–mediated effects on HCC cell stemness. Results MACC1-AS1 was highly expressed in HCC tissues and cells. MACC1-AS1 positively regulated the expression of stemness master regulators and inhibited spheroid-forming ability and ALDH1 activity. Furthermore, MACC1-AS1 promoted the stemness of HCC cells by antagonizing microRNA (miR)-145 activity. Overexpression of miR-145 also attenuated HCC cell stemness. Conclusions This work revealed a novel MACC1-AS1/miR-145 axis that regulates the stemness of HCC cells.

Matrix stiffness modulates inhibition of HCV replication by Fluvastatin in vitro

2013 ◽  
Vol 51 (01) ◽  
Author(s):  
J Kah ◽  
J Schrader ◽  
A Wüstenberg ◽  
G Tiegs ◽  
G Sass
Keyword(s):  
Matrix Stiffness

Protective Effect of Vitamin E on Immune Triggered, Granulocyte Mediated Endothelial Injury

1984 ◽  
Vol 51 (01) ◽  
pp. 089-092 ◽  
Author(s):  
M A Boogaerts ◽  
J Van de Broeck ◽  
H Deckmyn ◽  
C Roelant ◽  
J Vermylen ◽  
...  
Keyword(s):  
Vitamin E ◽  
Protective Effect ◽  
Umbilical Vein ◽  
Endothelial Damage ◽  
Endothelial Injury ◽  
Mediated Effects ◽  
Anti Oxidant ◽  
Endothelial Cell Cultures ◽  
Vitro Model

SummaryThe effect of alfa-tocopherol on the cell-cell interactions at the vessel wall were studied, using an in vitro model of human umbilical vein endothelial cell cultures (HUEC). Immune triggered granulocytes (PMN) will adhere to and damage HUEC and platelets enhance this PMN mediated endothelial injury. When HUEC are cultured in the presence of vitamin E, 51Cr-leakage induced by complement stimulated PMN is significantly decreased and the enhanced cytotoxicity by platelets is completely abolished (p <0.001).The inhibition of PMN induced endothelial injury is directly correlated to a diminished adherence of PMN to vitamin E- cultured HUEC (p <0.001), which may be mediated by an increase of both basal and stimulated endogenous prostacyclin (PGI2) from alfa-tocopherol-treated HUEC (p <0.025). The vitamin E-effect is abolished by incubation of HUEC with the irreversible cyclo-oxygenase inhibitor, acetylsalicylic acid, but the addition of exogenous PGI2 could not reproduce the vitamin E-mediated effects.We conclude that vitamin E exerts a protective effect on immune triggered endothelial damage, partly by increasing the endogenous anti-oxidant potential, partly by modulating intrinsic endothelial prostaglandin production. The failure to reproduce vitamin E-protection by exogenously added PGI2 may suggest additional, not yet elucidated vitamin E-effects on endothelial metabolism.

Cannabinoid Cb1 receptor-mediated effects on white and brown adipocytes

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
N Perwitz ◽  
B Meier ◽  
M Drenckhan ◽  
M Fasshauer ◽  
J Klein
Keyword(s):  
Cb1 Receptor ◽  
Cannabinoid Cb1 Receptor ◽  
Brown Adipocytes ◽  
Mediated Effects
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