{"database":"BioModels","file_versions":[],"scores":null,"additional":{"submitter":["Gautam Kumar"],"curationStatus":["Non-curated"],"modellingApproach":["other"],"levelVersion":["L2V1"],"full_dataset_link":["https://www.ebi.ac.uk/biomodels/MODEL2606190001"],"isPrivate":["false"],"repository":["BioModels"],"modelFormat":["SBML"],"omics_type":["Models"],"tokenised_name":["EGFR FGFR SIGNALLING"],"publication_year":["2026"],"submissionId":["MODEL2606190001"],"publication_authors":["Manasi Tukrul, Shailza Singh, Pooja Gulhane"],"first_author":["Manasi Tukrul"],"publication":["10.1038/s41540-026-00740-0,\n                            Non-small cell lung cancer (NSCLC), the predominant subtype of lung cancer, remains a major global health challenge due to its complex etiology and resistance to therapy. Aberrant signaling through receptor tyrosine kinases (RTKs) and mitogen-activated protein kinases (MAPKs) drives tumor progression and immune modulation, underscoring the need for systems-level investigation. In this study, we employed mathematical modeling and experimental validation to dissect the dynamic interplay of EGFR, FGFR, and TNFR signaling in NSCLC cells and macrophages. Our flux-based sensitivity analysis revealed persistent pathway biases, highlighting DUSP1, DUSP4, and SPRY2 as critical high-flux regulators within the MAPK and PI3K/AKT cascades. Crosstalk analysis demonstrated that these proteins form an interconnected signaling axis influencing cytokine production (IL6, IL10, IL12, and TNF-α) and macrophage-mediated responses in the tumor microenvironment. Functional assays confirmed that silencing SPRY2 suppressed DUSP1 and DUSP4 expression, impaired cell migration, and induced G2/M arrest, establishing a coordinated regulatory network essential for NSCLC progression. Together, our findings integrate computational modeling with molecular validation to identify DUSP1, DUSP4, and SPRY2 as pivotal drivers of oncogenic signaling and immune regulation. These proteins represent promising therapeutic targets whose inhibition may disrupt tumor-promoting feedback loops and attenuate NSCLC growth and survival.. 2026, null.\n                            1Biotechnology Research and Innovation Council- National Centre for Cell Science, NCCS\nComplex, Ganeshkhind, Pune-411007, INDIA\n2 Regional Centre for Biotechnology, Faridabad 121001, Haryana, India."],"submitter_mail":["gautamkumarlab9nb@gmail.com"],"publication_doi":["10.1038/s41540-026-00740-0"],"submitter_affiliation":["National Centre for cell science"],"additional_accession":[]},"is_claimable":false,"name":"EGFR-FGFR SIGNALLING","description":"EGFR, FGFR and TNFR signaling in NSCLC.","dates":{"last_modification":"2026-06-19","publication":"2026-06-27","submission":"2026-06-19"},"accession":"MODEL2606190001","cross_references":{"biomodels__db":["MODEL2606190001"],"doi":["10.1038/s41540-026-00740-0"]}}