Lung cancer is the most common cause of cancer mortality in Sweden and the overall prognosis is poor, with non-small cell lung cancer (NSCLC) representing 85% of all cases. Meanwhile, the underlying processes leading to clonal expansion and dissemination in NSCLC remains largely unknown. Expression analyses investigating differences between early and invasive lesions have mostly identified changes in the microenvironmental signaling network related to immune cell activation and extracellular matrix remodeling, rather than molecular changes specific for epithelial cells. Therefore, our work aims to identify regulatory signaling mechanisms between the tumor and stroma compartments during the progression of NSCLC, which will permit a refined risk- and treatment-stratification of patients but also identify novel therapeutic opportunities. With the in situ Proximity Ligation Assay (PLA)-technique (NaveniFlex, Navinci) we are able to investigate several different protein-protein interactions and protein phosphorylations believed to be of clinical significance in NSCLC.