scholarly journals The Reverse Warburg Effect Is Associated with Fbp2-Dependent Hif1α Regulation in Cancer Cells Stimulated by Fibroblasts

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 205 ◽  
Author(s):  
Przemysław Duda ◽  
Jakub Janczara ◽  
James A. McCubrey ◽  
Agnieszka Gizak ◽  
Dariusz Rakus
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Warburg Effect ◽  
Treatment Resistance ◽  
Lung Cancer Cells ◽  
Metabolic Coupling ◽  
Metabolic Conditions ◽  
A Cell ◽  
Lactate And Pyruvate ◽  
Reverse Warburg Effect

Fibroblasts are important contributors to cancer development. They create a tumor microenvironment and modulate our metabolism and treatment resistance. In the present paper, we demonstrate that healthy fibroblasts induce metabolic coupling with non-small cell lung cancer cells by down-regulating the expression of glycolytic enzymes in cancer cells and increasing the fibroblasts’ ability to release lactate and thus support cancer cells with energy-rich glucose-derived metabolites, such as lactate and pyruvate—a process known as the reverse Warburg effect. We demonstrate that these changes result from a fibroblasts-stimulated increase in the expression of fructose bisphosphatase (Fbp) in cancer cells and the consequent modulation of Hif1α function. We show that, in contrast to current beliefs, in lung cancer cells, the predominant and strong interaction with the Hif1α form of Fbp is not the liver (Fbp1) but in the muscle (Fbp2) isoform. Since Fbp2 oligomerization state and thus, its role is regulated by AMP and NAD+—crucial indicators of cellular metabolic conditions—we hypothesize that the Hif1α-dependent regulation of the metabolism in cancer is modulated through Fbp2, a sensor of the energy and redox state of a cell.

scholarly journals PolyI:C Suppresses TGF-β1-Induced Akt Phosphorylation and Reduces the Motility of A549 Lung Carcinoma Cells

2021 ◽  
Author(s):  
Takahiro Yamaguchi ◽  
Teizo Yoshimura ◽  
Toshiaki Ohara ◽  
Masayoshi Fujisawa ◽  
Gao Tong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Cell Invasion ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Mesenchymal Transition ◽  
Akt Phosphorylation ◽  
Polycytidylic Acid ◽  
A Cell ◽  
Tgf Β1

Abstract Backgrounds: Transforming growth factor (TGF)-β is shown to play a critical role in cancer progression by inducing epithelial mesenchymal transition (EMT). Polyinosinic-polycytidylic acid (polyI:C), a synthetic agonist for toll-like receptor (TLR) 3, has been successfully used to treat some cancer patients as a vaccine adjuvant, but its direct action on the proliferation or migration of cancer cells, such as lung cancer cells, undergoing EMT remains unknown. Methods and results: By an in vitro cell proliferation assay, polyI:C showed no effect on the growth of TGF-β1-treated A549 human lung cancer cells at the concentration range up to 10 mg/ml; however, it markedly suppressed the motility in a cell scratch and a cell invasion assay. By Western blotting, polyI:C dramatically decreased TGF-β1-induced Ak strain transforming (Akt) phosphorylation and increased phosphatase and tensin homologue (PTEN) expression without affecting the Son of mothers against decapentaplegic (Smad) 3 phosphorylation or the expression level of E-cadherin, N-cadherin or Snail, indicating that polyI:C suppressed cell motility independently of the ‘cadherin switching’. The Akt inhibitor perifosine inhibited TGF-β1-induced cell invasion, and the PTEN-specific inhibitor VO-OHpic appeared to reverse the inhibitory effect of polyI:C. Conclusion: Our results indicate that polyI:C has the capacity to suppress the motility of TGF-β1-treated A549 cells by targeting the phosphatidylinositol 3-kinase /Akt pathway partly via PTEN and suggest that polyI:C may be used to prevent or reduce the metastasis of lung cancer cells.

scholarly journals ALK inhibition activates LC3B-independent, protective autophagy in EML4-ALK positive lung cancer cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anna M. Schläfli ◽  
Igor Tokarchuk ◽  
Sarah Parejo ◽  
Susanne Jutzi ◽  
Sabina Berezowska ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Surrogate Marker ◽  
Treatment Resistance ◽  
Lung Cancer Cells ◽  
Marker Proteins ◽  
Cancer Cell Survival ◽  
Autophagic Activity ◽  
Alk Positive ◽  
The Impact

AbstractALK inhibitors effectively target EML4-ALK positive non-small cell lung cancer, but their effects are hampered by treatment resistance. In the present study, we asked whether ALK inhibition affects autophagy, and whether this may influence treatment response. Whereas the impact of targeted therapies on autophagic activity previously have been assessed by surrogate marker proteins such as LC3B, we here thoroughly examined effects on functional autophagic activity, i.e. on the sequestration and degradation of autophagic cargo, in addition to autophagic markers. Interestingly, the ALK inhibitor Ceritinib decreased mTOR activity and increased GFP-WIPI1 dot formation in H3122 and H2228 EML4-ALK+ lung cancer cells, suggesting autophagy activation. Moreover, an mCherry-EGFP-LC3B based assay indicated elevated LC3B carrier flux upon ALK inhibition. In accordance, autophagic cargo sequestration and long-lived protein degradation significantly increased upon ALK inhibition. Intriguingly, autophagic cargo flux was dependent on VPS34 and ULK1, but not LC3B. Co-treating H3122 cells with Ceritinib and a VPS34 inhibitor or Bafilomycin A1 resulted in reduced cell numbers. Moreover, VPS34 inhibition reduced clonogenic recovery of Ceritinib-treated cells. In summary, our results indicate that ALK inhibition triggers LC3B-independent macroautophagic flux in EML4-ALK+ cells to support cancer cell survival and clonogenic growth.

A cell membrane vehicle co-delivering sorafenib and doxorubicin remodel the tumor microenvironment and enhance immunotherapy by inducing immunogenic cell death in lung cancer cells

2020 ◽  
Vol 8 (34) ◽  
pp. 7755-7765 ◽  
Author(s):  
Jun Wan ◽  
Jian Wang ◽  
Min Zhou ◽  
Zhanpeng Rao ◽  
Xiean Ling
Keyword(s):  
Lung Cancer ◽  
Cell Death ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Cell Membrane ◽  
Cancer Cells ◽  
Cancer Immunotherapy ◽  
Lung Cancer Cells ◽  
Immunogenic Cell Death ◽  
A Cell

Cancer immunotherapy is a promising approach for cancer therapy but is usually hindered by the inhibition of the tumor microenvironment (TME).

Inhibitory effects of Actinidia Chinensis planch root extracts (acRoots) on human lung cancer cells through retinoic acid receptor beta

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Lingyan Wang ◽  
Jiayun Hou ◽  
Minghuan Zheng ◽  
Lin Shi
Keyword(s):  
Lung Cancer ◽  
Cancer Cells ◽  
Human Lung ◽  
Retinoic Acid Receptor ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Inhibitory Effects ◽  
The Core ◽  
Human Lung Cancer Cells ◽  
Receptor Beta

Actinidia Chinensis Planch roots (acRoots) are used to treat many cancers, although the anti-tumor mechanism by which acRoots inhibit cancer cell growth remains unclear. The present study aims at investigating inhibitory effects of acRoots on human lung cancer cells and potential mechanisms. Our data demonstrate that the inhibitory effects of acRoots on lung cancer cells depend on genetic backgrounds and phenotypes of cells. We furthermore found the expression of metabolism-associated gene profiles varied between acRoots-hypersensitive (H460) or hyposensitive lung cancer cells (H1299) after screening lung cancer cells with different genetic backgrounds. We selected retinoic acid receptor beta (RARB) as the core target within metabolism-associated core gene networks and evaluated RARB changes and roles in cells treated with acRoots at different concentrations and timeframes. Hypersensitive cancer cells with the deletion of RARB expression did not response to the treatment with acRoots, while RARB deletion did not change effects of acRoots on hyposensitive cells. Thus, it seems that RARB as the core target within metabolism-associated networks plays important roles in the regulation of lung cancer cell sensitivity to acRoots.

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