Tension in tumour cells keeps metabolism high

Ayad, Nadia; Weaver, Valerie M.

doi:10.1038/d41586-020-00314-y

Cited by 11 publications

(9 citation statements)

References 17 publications

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“… 2 Hypoxic niche and immune microenvironment are regarded as two vital specialized microenvironments that can reprogram cancer biology in various aspects and serve as a potential target for cancer therapy, especially targeted therapy and immunotherapy. 12 – 17 Many studies have confirmed that metabolism microenvironment, 18 – 21 acidic niche, 22 – 24 innervated niche in TME 25 – 31 and mechanical niche 32 – 37 remarkably affect cancer development. However, these specialized microenvironments are arranged in a crisscross pattern, suggesting the necessity to recognize the function of each microenvironment and the crosstalk among one another (Fig.…”

Section: Persistent Updating Concept Of Tmementioning

confidence: 99%

“…Mechanical microenvironment is another newly investigated specialized microenvironment. 32 , 34 , 36 Its formation relies largely on intracellular components (vimentin, actin, and neurofilaments), extracellular components (collagen and fibrin), intercellular signaling (integrin), and stromal cells (fibroblasts). 127 CAFs secrete matrix metalloproteinases (MMPs) including MMP2, MMP3, and MMP9 or activate yes-associated protein to promote ECM degradation and remodeling, epithelial-mesenchymal transition, and cancer-stem-cell stemness.…”

Section: Hallmarks Of Tmementioning

confidence: 99%

“…They also demonstrated that the stiffness of cancer cells promotes their maintenance of fast metabolism, thereby further elucidating the heterogeneous specialized TME. 32 …”

Section: Hallmarks Of Tmementioning

confidence: 99%

See 2 more Smart Citations

The updated landscape of tumor microenvironment and drug repurposing

Jin

2020

Sig Transduct Target Ther

732

483

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Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly benefit further studies exploring effective treating methods. Herein, we present an updated image of TME with emphasis on hypoxic niche, immune microenvironment, metabolism microenvironment, acidic niche, innervated niche, and mechanical microenvironment. We then summarize conventional drugs including aspirin, celecoxib, β-adrenergic antagonist, metformin, and statin in new antitumor application. These drugs are considered as viable candidates for combination therapy due to their antitumor activity and extensive use in clinical practice. We also provide our outlook on directions and potential applications of TME theory. This review depicts a comprehensive and vivid landscape of TME from biology to treatment.

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Section: Persistent Updating Concept Of Tmementioning

confidence: 99%

Section: Hallmarks Of Tmementioning

confidence: 99%

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The updated landscape of tumor microenvironment and drug repurposing

Jin

2020

Sig Transduct Target Ther

732

483

View full text Add to dashboard Cite

show abstract

“…In recent years, mechanical microenvironment has been found to have an important relationship with the occurrence and development of tumors, which is another special microenvironment that has been studied in recent years ( 96 ) ( Figure 4 ). There are indications that the tumor exhibits a higher cell density, making it stiffer and significantly different from normal tissue ( 97 ).…”

Section: Other Tumor Microenvironments and Statinsmentioning

confidence: 99%

Targeting the Tumor Microenvironment: A Literature Review of the Novel Anti-Tumor Mechanism of Statins

et al. 2021

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Statins is widely used in clinical practice as lipid-lowering drugs and has been proven to be effective in the treatment of cardiovascular, endocrine, metabolic syndrome and other diseases. The latest preclinical evidence shows that statins have anti-proliferation, pro-apoptotic, anti-invasion and radiotherapy sensitization effects on tumor cells, suggesting that statins may become a new type of anti-tumor drugs. For a long time, mevalonate pathway has been proved to play a supporting role in the development of tumor cells. As an effective inhibitor of mevalonate pathway, statins have been proved to have a direct auxiliary anti-tumor effect in a large number of studies. In addition, anti-tumor effects of statins through ferroptosis, pyroptosis, autophagy and tumor microenvironment (TME) have also been gradually discovered. However, the specific mechanism of the antitumor effect of statins in the tumor microenvironment has not been clearly elucidated. Herein, we reviewed the antitumor effects of statins in tumor microenvironment, focusing on hypoxia microenvironment, immune microenvironment, metabolic microenvironment, acid microenvironment and mechanical microenvironment.

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“…Recent studies have focused on the relationship between the extracellular environment and metabolism, finding that mechanical signals promote oncogenesis and change cellular metabolism, and that in epithelial cells [3], placement in a stiff matrix upregulates the key glycolytic protein phosphofructokinase, thereby increasing glycolysis [4]. It is reported that the Hippo pathway and its effector yes-associated protein (YAP) are important for stellate cell activation [5].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Alterations in Spheroid-Cultured Hepatic Stellate Cells

Fujisawa

Takami

Sasai

et al. 2020

IJMS

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Hepatic stellate cells (HSCs) play a vital role in liver fibrosis, and a greater understanding of their regulation is required. Recent studies have focused on relationships between extracellular matrix (ECM) stiffness and gene expression or cellular metabolism, but none have provided a detailed metabolic analysis of HSC changes in spheroid cultures. Accordingly, in the present study, we created an HSC spheroid culture and analyzed changes in gene expression and metabolism. Expression of α-smooth muscle actin (α-SMA) decreased in the spheroids, suppressing proliferation. Gene expression analysis revealed the cell cycle, sirtuin signaling, mitochondrial dysfunction, and the Hippo pathway to be canonical pathways, believed to result from decreased proliferative ability or mitochondrial suppression. In the Hippo pathway, nuclear translocation of the yes-associated protein (YAP) was decreased in the spheroid, which was associated with the stiffness of the ECM. Metabolome analysis showed glucose metabolism changes in the spheroid, including glutathione pathway upregulation and increased lipid synthesis. Addition of the glycolytic product phosphoenolpyruvate (PEP) led to increased spheroid size, with increased expression of proteins such as α-SMA and S6 ribosomal protein (RPS6) phosphorylation, which was attributed to decreased suppression of translation. The results of our study contribute to the understanding of metabolic changes in HSCs and the progression of hepatic fibrosis.

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Tension in tumour cells keeps metabolism high

Cited by 11 publications

References 17 publications

The updated landscape of tumor microenvironment and drug repurposing

The updated landscape of tumor microenvironment and drug repurposing

Targeting the Tumor Microenvironment: A Literature Review of the Novel Anti-Tumor Mechanism of Statins

Metabolic Alterations in Spheroid-Cultured Hepatic Stellate Cells

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