Non-small cell lung cancer map and analysis: exploring interconnected oncogenic signal integrators

Area of Science:

• Molecular biology
• Systems biology
• Cancer research

Background:

• Non-Small Cell Lung Cancer (NSCLC) is a leading cause of cancer mortality, with metastasis present at diagnosis in 30-40% of patients.
• Epithelial to Mesenchymal Transition (EMT) is a key process in cancer progression and metastasis, significantly influenced by Transforming Growth Factor-β (TGFβ) signaling.

Purpose of the Study:

• To construct a comprehensive molecular interaction map of TGFβ-induced EMT in NSCLC.
• To analyze the complex regulatory dynamics and identify key regulators involved in NSCLC metastasis.

Main Methods:

• Extensive literature survey to build a molecular interaction map (394 species, 554 reactions).
• Utilized Cell Designer, SBGN, SBML standards for map construction.
• Employed logical modeling (CaSQ) and dynamic analysis (Cell Collective) for simulation and validation.

Main Results:

• The developed map details TGFβ-induced EMT pathways, including SMAD-dependent and independent signaling (PI3K/Akt, Wnt, EGFR, JAK/STAT, p38 MAPK, NOTCH, Hypoxia).
• Dynamic analysis captured known experimental outcomes, including the hybrid EMT phenotype crucial for metastatic plasticity.
• Network and transcriptome analyses identified prognostic and clinically relevant hub regulators.

Conclusions:

• The study provides a detailed molecular map and dynamic analysis of TGFβ-induced EMT in NSCLC.
• Identified critical regulators and network properties governing EMT and metastasis.
• Offers a deeper understanding of the regulatory network driving NSCLC progression and metastasis.