{"doi":"10.3389/fcell.2024.1459926","title":"Editorial: Deregulated signaling pathways in inflammation and cancer","abstract":"Signaling pathways govern how cells survive, proliferate, communicate and respond to their environment. Alterations in signaling pathways can lead to dysregulated immune and inflammatory responses or uncontrolled cell growth. Unresolved inflammation is an underlying cause of many diseases including cancer (1,2) In both inflammation and cancer, dysregulation of one or more signaling pathways involving altered transcription, translation, posttranscriptional and posttranslational regulations, mutations affecting protein and nucleic acid functions as well as epigenetic modifications are associated with the pathology of the disease. Hence, understanding deregulated signaling mechanisms that leads to the disease condition is necessary to develop targeted therapeutics with minimal off-target effects. Deciphering deregulated signaling pathways will contribute to the development of early intervention therapies, identification of altered gene expression that may serve as potential biomarkers and reveal novel targets for combination therapy. This research topic comprises a diverse set of six comprehensive reviews and an original article covering selected signaling pathways involved in inflammation and cancer. The original research article by Hernandez-Cano et al., presents key findings on the role of C3G (RapGEF1) in plateletdependent angiogenesis and tumor metastasis. This study suggests that C3G expression should be tightly regulated in platelets and megakaryocytes to prevent megakaryocytosis, thrombocytosis and myeloproliferative disorders. Further, suggesting a global signaling role of C3G, preliminary experiments presented show that absence of C3G in platelets compromised proteasomal and lysosomal degradation, which may allow the sustained expression of many proteins involved in inflammation and cancer.Each of the review article has diligently compiled information from over hundred other articles to provide insightful updates on the respective subject areas discussed. The reviews by Hu et al., and Deng et al., focus on liver and intestinal inflammation, respectively. Hu et al., have summarized the signaling roles of TRIF protein, a crucial adaptor molecule downstream of tolllike receptors 3 (TLR3) and 4 (TLR4). Notably, specific roles TRIF in multiple signaling pathways emanating from TLR3 and TLR4 are discussed along with an in-depth discussion on the role of TRIF in various hepatic inflammatory diseases as well as liver cancer and fibrosis. The detailed description of biochemical mechanisms involving TRIF and its link to pathologies successfully presents the potential to target TRIF and associated pathways to treat liver diseases.Hippo pathway with specific focus on intestinal diseases and intestinal cancer. Elaborate discussions are included on the roles of Hippo pathway in metabolism, immune response, mucosal barrier, mechanical stress and intestinal tumors. Similarly, the roles of ferroptosis, a regulated cell death resulting from iron accumulation (3), in inflammation, immune response, cancer, metabolism and mechanotransduction are also discussed. Interestingly, attention has been drawn to the overlapping roles of Hippo pathway and ferroptosis in intestinal diseases, by specifically calling out potential mediators that bridge these pathways. These include GPX4, ROS, gut microbiota, p53 and YAP among several others. In conclusion, the authors have correctly acknowledged that current research on the importance of Hippo pathway and ferroptosis is confined to intestine and future studies are warranted to expand this to diseases of other organs as well.The reviews by Wei et al., and Le focus on inflammation and cancer. Wei et al., elaborated the mechanisms involving two reciprocal regulators of inflammation: the anti-inflammatory histone deacetylase SIRT1 and the pro-inflammatory HMGB1. The authors have compendiously presented the functions of SIRT1 and HMGB1 in various inflammatory conditions and cancers alluding to the cross talk","journal":"Frontiers in Cell and Developmental Biology","year":2024,"id":501211,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9586,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":326799,"name":"Parameswaran Ramakrishnan","orcid":"0000-0002-1314-827X","position":0,"is_corresponding":true}],"reference_count":3,"raw_metadata":null,"created_at":"2026-07-19T02:10:12.068207Z","pmid":"39100093","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}