Table 1.

Main pathologic mechanisms contributing to the development of lung cancer and pulmonary fibrosis based on refs. [2,6,10,16,17,18,19,21,23,25,26,27,28,29,30,31,33,34,35,37,38,39,40,41]. For further explanation, see text.

Smoking Genetic susceptibility 2nd hit injury Chronic inflammation Aging	Gene mutations	P53 Surfactant protein genes JAK Fragile histidine triads Microsatellite instability Telomere shortening and expression (TERT, TERC) MET
	Signaling pathways	Tyrosine kinase signaling Hypermethylation of the CD90/Thy-1 promoter PD-1/PDL-1 MET upregulation
	Epithelial-mesenchymal transition	TGF-β Matrix metalloproteases
	Cell migration and invasion	Laminin Heat shock protein 27 Fasciin Matrix metalloproteases Integrins Intercellular channels formed by connexins (Cxs)
	Cellular senescence	Senescence-associated secretory phenotype (SASP)

P53: cellular tumor antigen p53; JAK: Janus kinase; TERT: telomerase reverse transcriptase; TERC: telomerase RNA component; MET: mesenchymal–epithelial transforming factor proto-oncogene; CD90/Thy-1: cluster of differentiation 90/Thymocyte differentiation antigen-1; PD-1: programmed cell death protein 1; PDL-1: programmed death ligand-1; TGF-β: transforming growth factor β.