scholarly journals High Mobility Group Box 1 (HMGB1) Induces Toll-Like Receptor 4-Mediated Production of the Immunosuppressive Protein Galectin-9 in Human Cancer Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Anette Teo Hansen Selnø ◽  
Stephanie Schlichtner ◽  
Inna M. Yasinska ◽  
Svetlana S. Sakhnevych ◽  
Walter Fiedler ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Transforming Growth Factor Beta ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
High Mobility ◽  
High Mobility Group ◽  
Toll Like Receptor ◽  
Autocrine Loop ◽  
Human Cancer Cells

High mobility group box 1 (HMGB1) is a non-histone protein which is predominantly localised in the cell nucleus. However, stressed, dying, injured or dead cells can release this protein into the extracellular matrix passively. In addition, HMGB1 release was observed in cancer and immune cells where this process can be triggered by various endogenous as well as exogenous stimuli. Importantly, released HMGB1 acts as a so-called “danger signal” and could impact on the ability of cancer cells to escape host immune surveillance. However, the molecular mechanisms underlying the functional role of HMGB1 in determining the capability of human cancer cells to evade immune attack remain unclear. Here we report that the involvement of HMGB1 in anti-cancer immune evasion is determined by Toll-like receptor (TLR) 4, which recognises HMGB1 as a ligand. We found that HGMB1 induces TLR4-mediated production of transforming growth factor beta type 1 (TGF-β), displaying autocrine/paracrine activities. TGF-β induces production of the immunosuppressive protein galectin-9 in cancer cells. In TLR4-positive cancer cells, HMGB1 triggers the formation of an autocrine loop which induces galectin-9 expression. In malignant cells lacking TLR4, the same effect could be triggered by HMGB1 indirectly through TLR4-expressing myeloid cells present in the tumour microenvironment (e. g. tumour-associated macrophages).

scholarly journals Mutational activation of BRAF confers sensitivity to transforming growth factor beta inhibitors in human cancer cells

Oncotarget ◽  
2016 ◽  
Vol 7 (50) ◽  
pp. 81995-82012 ◽  
Author(s):  
Lindsay C. Spender ◽  
G. John Ferguson ◽  
Sijia Liu ◽  
Chao Cui ◽  
Maria Romina Girotti ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cancer Cells ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Growth Factor Beta ◽  
Mutational Activation

Molecular mechanisms of G0/G1 cell-cycle arrest and apoptosis induced by terfenadine in human cancer cells

2003 ◽  
Vol 37 (1) ◽  
pp. 39-50 ◽  
Author(s):  
Jean-Dean Liu ◽  
Ying-Jan Wang ◽  
Chien-Ho Chen ◽  
Cheng-Fei Yu ◽  
Li-Ching Chen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
Cycle Arrest ◽  
G1 Cell Cycle Arrest

scholarly journals RuvBL1 Maintains Resistance to TRAIL-Induced Apoptosis by Suppressing c-Jun/AP-1 Activity in Non-Small Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Hao Li ◽  
Taoran Zhou ◽  
Yue Zhang ◽  
Hengyi Jiang ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Therapeutic Strategy ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Human Cancer Cells ◽  
The Common ◽  
Trail Resistance ◽  
Induced Apoptosis ◽  
Necrosis Factor

Lung cancer is the common malignant tumor with the highest death rate in the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a potential anticancer agent induces selective apoptotic death of human cancer cells. Unfortunately, approximately half of lung cancer cell lines are intrinsically resistant to TRAIL-induced cell death. In this study, we identified RuvBL1 as a repressor of c-Jun/AP-1 activity, contributing to TRAIL resistance in lung cancer cells. Knocking down RuvBL1 effectively sensitized resistant cells to TRAIL, and overexpression of RuvBL1 inhibited TRAIL-induced apoptosis. Moreover, there was a negative correlation expression between RuvBL1 and c-Jun in lung adenocarcinoma by Oncomine analyses. High expression of RuvBL1 inversely with low c-Jun in lung cancer was associated with a poor overall prognosis. Taken together, our studies broaden the molecular mechanisms of TRAIL resistance and suggest the application of silencing RuvBL1 synergized with TRAIL to be a novel therapeutic strategy in lung cancer treatment.

scholarly journals The molecular mechanisms of Aloin induce gastric cancer cells apoptosis by targeting High Mobility Group Box 1

2019 ◽  
Vol Volume 13 ◽  
pp. 1221-1231 ◽  
Author(s):  
Hong Tao ◽  
Tuo Tang ◽  
Shengnan Wang ◽  
Ziqian Wang ◽  
Yunfei Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Cells ◽  
Molecular Mechanisms ◽  
High Mobility ◽  
High Mobility Group ◽  
Gastric Cancer Cells

scholarly journals Cytotoxicity of portoamides in human cancer cells and analysis of the molecular mechanisms of action

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0188817 ◽  
Author(s):  
Tiago Ribeiro ◽  
Filipa Lemos ◽  
Marco Preto ◽  
Joana Azevedo ◽  
Maria Lígia Sousa ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Mechanisms Of Action ◽  
Human Cancer Cells

scholarly journals Requirement for the SnoN Oncoprotein in Transforming Growth Factor β-Induced Oncogenic Transformation of Fibroblast Cells

2005 ◽  
Vol 25 (24) ◽  
pp. 10731-10744 ◽  
Author(s):  
Qingwei Zhu ◽  
Sonia Pearson-White ◽  
Kunxin Luo
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Human Cancer ◽  
Transforming Growth Factor Β ◽  
Lymphoid Cells ◽  
Human Cancer Cells ◽  
Inhibitory Site ◽  
Transforming Activity

ABSTRACT Transforming growth factor β (TGF-β) was originally identified by virtue of its ability to induce transformation of the AKR-2B and NRK fibroblasts but was later found to be a potent inhibitor of the growth of epithelial, endothelial, and lymphoid cells. Although the growth-inhibitory pathway of TGF-β mediated by the Smad proteins is well studied, the signaling pathway leading to the transforming activity of TGF-β in fibroblasts is not well understood. Here we show that SnoN, a member of the Ski family of oncoproteins, is required for TGF-β-induced proliferation and transformation of AKR-2B and NRK fibroblasts. TGF-β induces upregulation of snoN expression in both epithelial cells and fibroblasts through a common Smad-dependent mechanism. However, a strong and prolonged activation of snoN transcription that lasts for 8 to 24 h is detected only in these two fibroblast lines. This prolonged induction is mediated by Smad2 and appears to play an important role in the transformation of both AKR-2B and NRK cells. Reduction of snoN expression by small interfering RNA or shortening of the duration of snoN induction by a pharmacological inhibitor impaired TGF-β-induced anchorage-independent growth of AKR-2B cells. Interestingly, Smad2 and Smad3 play opposite roles in regulating snoN expression in both fibroblasts and epithelial cells. The Smad2/Smad4 complex activates snoN transcription by direct binding to the TGF-β-responsive element in the snoN promoter, while the Smad3/Smad4 complex inhibits it through a novel Smad inhibitory site. Mutations of Smad4 that render it defective in heterodimerization with Smad3, which are found in many human cancers, convert the activity of Smad3 on the snoN promoter from inhibitory to stimulatory, resulting in increased snoN expression in cancer cells. Thus, we demonstrate a novel role of SnoN in the transforming activity of TGF-β in fibroblasts and also uncovered a mechanism for the elevated SnoN expression in some human cancer cells.

EGFR signal transactivation in cancer cells

2003 ◽  
Vol 31 (6) ◽  
pp. 1203-1208 ◽  
Author(s):  
O.M. Fischer ◽  
S. Hart ◽  
A. Gschwind ◽  
A. Ullrich
Keyword(s):  
Growth Factor ◽  
Cancer Cells ◽  
Cross Talk ◽  
Molecular Mechanisms ◽  
Human Cancer ◽  
Growth Factor Receptor ◽  
Cell Types ◽  
General Concept ◽  
Human Carcinoma ◽  
Human Cancer Cells

The EGFR (epidermal growth factor receptor) plays a key role in the regulation of essential normal cellular processes and in the pathophysiology of hyperproliferative diseases such as cancer. Recent investigations have demonstrated that GPCRs (G-protein-coupled receptors) are able to utilize the EGFR as a downstream signalling partner in the generation of mitogenic signals. This cross-talk mechanism combines the broad diversity of GPCRs with the signalling capacities of the EGFR and has emerged as a general concept in a multitude of cell types. The molecular mechanisms of EGFR signal transactivation involve processing of transmembrane growth factor precursors by metalloproteases which have been recently identified as members of the ADAM (adisintegrin and metalloprotease) family of zinc-dependent proteases. Subsequently, the EGFR transmits signals to prominent downstream pathways, such as mitogen-activated protein kinases, the phosphoinositide 3-kinase/Akt pathway and modulation of ion channels. Analysis of GPCR-induced EGFR activation in more than 60 human carcinoma cell lines derived from different tissues has demonstrated the broad relevance of this signalling mechanism in cancer. Moreover, EGFR signal transactivation was linked to diverse biological processes in human cancer cells, such as cell proliferation, migration and anti-apoptosis. Together with investigations revealing the importance of this GPCR–EGFR cross-talk mechanism in cardiac hypertrophy, Helicobacter pylori-induced pathophysiological processes and cystic fibrosis, these findings support an important role for GPCR ligand-dependent EGFR signal transactivation in diverse pathophysiological disorders.

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