Importance of TNF-alpha and its alterations in the development of cancers

Sharif, Pouya Mahdavi; Jabbari, Parnian; Razi, Sepideh; Keshavarz-Fathi, Mahsa; Rezaei, Nima

doi:10.1016/j.cyto.2020.155066

Cited by 43 publications

(12 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As expected, TNF (TNF‐α) occupied the central position in the network, indicating its close associations with the other proteins. TNF‐α belongs to the TNF superfamily of cytokines, which regulates dozens of pathways related to cell proliferation, differentiation, survival, and death 155 . Following, IL‐6, NFκB1, CASPs, and MAPKs have previously all been selected as pivotal targets of berberine, and will not be discussed further here.…”

Section: Resultsmentioning

confidence: 99%

A small molecule compound berberine as an orally active therapeutic candidate against COVID‐19 and SARS: A computational and mechanistic study

Wang

Maskey

et al. 2021

The FASEB Journal

View full text Add to dashboard Cite

The novel coronavirus disease, COVID-19, has grown into a global pandemic and a major public health threat since its breakout in December 2019. To date, no specific therapeutic drug or vaccine for treating COVID-19 and SARS has been FDA approved. Previous studies suggest that berberine, an isoquinoline alkaloid, has shown various biological activities that may help against COVID-19 and SARS, including antiviral, anti-allergy and inflammation, hepatoprotection against drug-and infectioninduced liver injury, as well as reducing oxidative stress. In particular, berberine has a wide range of antiviral activities such as anti-influenza, anti-hepatitis C, anticytomegalovirus, and anti-alphavirus. As an ingredient recommended in guidelines issued by the China National Health Commission for COVID-19 to be combined with other therapy, berberine is a promising orally administered therapeutic candidate against SARS-CoV and SARS-CoV-2. The current study comprehensively evaluates the potential therapeutic mechanisms of berberine in preventing and treating COVID-19 and SARS using computational modeling, including target mining, gene ontology enrichment, pathway analyses, protein-protein interaction analysis, and 2 of 19 | WANG et Al. 1 | INTRODUCTION Coronavirus disease-19 (COVID-19) is an infectious disease caused by a newly discovered coronavirus SARS-CoV2 that has reached global pandemic status and become a major global health threat. As of December 1 2020, there have been 63,751,931 confirmed cases and 1,477,976 deaths worldwide. 1 The United States hit record-high daily COVID-19 cases in November, 2020. Since the pandemic started in March, 2020, the nation has surpassed 12 million cases and more than 266,000 Americans have died. United States could see "a surge upon a surge" of COVID-19 cases this winter. 2 During just two full days at the end of November, 2020, the country saw over 360,000 new COVID-19 cases nationwide, in addition to over 2,700 new deaths. In 2003, a zoonotic coronavirus outbreak of SARS-CoV had resulted in severe SARS with fatality rates of 10%. 3-6 The SARS-CoV-2 genome shares approximately 70%-80% sequence similarity to SARS-CoV, and causes similar clinical symptoms. 7,8 Key clinical features of COVID-19 and SARS include fever, chills, muscle pain, headache, sore throat, new loss of taste or smell, cough, shortness of breath, gastrointestinal problems in mild to moderate cases, and more serious disease involving pneumonia, acute respiratory distress syndrome, cardiovascular and hepatic failure with high morbidity. 7,8 Individuals with pre-existing conditions like cardiovascular disease, hypertension, asthma, and diabetes, 9 and elderly patients are at a higher risk to become infected with severe symptoms. 10 To date, no specific therapeutic drug or vaccine COVID-19 and SARS is available, resulting in an urgent need for broad-spectrum therapeutics for COVID-19 and other CoV infections.

show abstract

Section: Resultsmentioning

confidence: 99%

A small molecule compound berberine as an orally active therapeutic candidate against COVID‐19 and SARS: A computational and mechanistic study

Wang

Maskey

et al. 2021

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…Previous studies have identified links between SHMT proteins and interferon signaling, and these findings indicate SHMT expression is associated with immune response transcriptional programs in ACC and LGG patient cohorts. ,, Tumor necrosis factor alpha (TNF-α) is a key cytokine that regulates immune responses in healthy persons and in diseased conditions. In cancer, TNF-α can elicit myriad effects depending on the context, such as proliferation, apoptosis, necrosis, migration, angiogenesis, or invasion . Little is known about the relationship between cancer cell metabolism reprogramming and TNF-α signaling through NF-κB.…”

Section: Shmt2mentioning

confidence: 99%

A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight

Cuthbertson

Arabzada

Bankhead

et al. 2021

ACS Pharmacol. Transl. Sci.

View full text Add to dashboard Cite

Metabolic reprogramming is a key hallmark of cancer and shifts cellular metabolism to meet the demands of biomass production necessary for abnormal cell reproduction. One-carbon metabolism (1CM) contributes to many biosynthetic pathways that fuel growth and is comprised of a complex network of enzymes. Methotrexate and 5-fluorouracil were pioneering drugs in this field and are still widely used today as anticancer agents as well as for other diseases such as arthritis. Besides dihydrofolate reductase and thymidylate synthase, two other enzymes of the folate cycle arm of 1CM have not been targeted clinically: serine hydroxymethyltransferase (SHMT) and methylenetetrahydrofolate dehydrogenase (MTHFD). An increasing body of literature suggests that the mitochondrial isoforms of these enzymes (SHMT2 and MTHFD2) are clinically relevant in the context of cancer. In this review, we focused on the 1CM pathway as a target for cancer therapy and, in particular, SHMT2 and MTHFD2. The function, regulation, and clinical relevance of SHMT2 and MTHFD2 are all discussed. We expand on previous clinical studies and evaluate the prognostic significance of these critical enzymes by performing a pan-cancer analysis of patient data from the The Cancer Genome Atlas and a transcriptional coexpression network enrichment analysis. We also provide an overview of preclinical and clinical inhibitors targeting the folate pathway, the methionine cycle, and folate-dependent purine biosynthesis enzymes.

show abstract

“…Intriguingly, our data not only uncover potential cancer cell-autonomous transcriptional programs encoded by KRAS-TP53 co-alteration that orchestrate innate immune cell trafficking, but also implicate granulocyte-derived inflammasome and TNF signaling as novel functional regulators of the dynamic immune-tumor-stromal crosstalk in the TME that sustain innate immunoregulatory signaling in KRAS-TP53 co-altered tumor cells. Indeed, emerging evidence highlights the paradoxical pro-tumorigenic roles of both inflammasome and TNF signaling in cancer initiation and progression [56, 57]. Furthermore, our lineage trajectory reconstruction in single-cell intratumoral gMDSC transcriptomes identify distinct granulocytic developmental fates associated with Tnf signaling, and provides a molecular roadmap for interception strategies aimed at disrupting gMDSC compartment-specific TNF signaling in PDAC.…”

Section: Discussionmentioning

confidence: 93%

Distinct Mechanisms of Innate and Adaptive Immune Regulation Underlie Poor Oncologic Outcomes Associated with KRAS-TP53 Co-Alteration in Pancreatic Cancer

Datta

Bianchi

Silva

et al. 2022

Preprint

View full text Add to dashboard Cite

Co-occurrent KRAS and TP53 mutations define a majority of patients with pancreatic ductal adenocarcinoma (PDAC) and define its pro-metastatic proclivity. Here, we demonstrate that KRAS-TP53 co-alteration is associated with worse survival compared with either KRAS-alone or TP53-alone altered PDAC in 245 patients with metastatic disease treated at a tertiary referral cancer center, and validate this observation in two independent molecularly annotated datasets. Compared with non-TP53 mutated KRAS-altered tumors, KRAS-TP53 co-alteration engenders disproportionately innate immune-enriched and CD8+ T-cell-excluded immune signatures. Leveraging in silico, in vitro, and in vivo models of human and murine PDAC, we discover a novel intersection between KRAS-TP53 co-altered transcriptomes, TP63-defined squamous trans-differentiation, and myeloid-cell migration into the tumor microenvironment. Comparison of single-cell transcriptomes between KRAS-TP53 co-altered and KRAS-altered/TP53WT tumors revealed cancer cell-autonomous transcriptional programs that orchestrate innate immune trafficking and function. Moreover, we uncover granulocyte-derived inflammasome activation and TNF signaling as putative paracrine mediators of innate immunoregulatory transcriptional programs in KRAS-TP53 co-altered PDAC. Immune subtyping of KRAS-TP53 co-altered PDAC reveals conflation of intratumor heterogeneity with progenitor-like stemness properties. Coalescing these distinct molecular characteristics into a KRAS-TP53 co-altered "immunoregulatory program" predicts chemoresistance in metastatic PDAC patients enrolled in the COMPASS trial, as well as worse overall survival.

show abstract

Importance of TNF-alpha and its alterations in the development of cancers

Cited by 43 publications

References 168 publications

A small molecule compound berberine as an orally active therapeutic candidate against COVID‐19 and SARS: A computational and mechanistic study

A small molecule compound berberine as an orally active therapeutic candidate against COVID‐19 and SARS: A computational and mechanistic study

A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight

Distinct Mechanisms of Innate and Adaptive Immune Regulation Underlie Poor Oncologic Outcomes Associated with KRAS-TP53 Co-Alteration in Pancreatic Cancer

Contact Info

Product

Resources

About