HSIN-HAN HOUPan, Huei-JyuanHuei-JyuanPanWEI-YU LIAOLee, Chau-HwangChau-HwangLeeCHONG-JEN YU2020-07-212020-07-2120200020-7136https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087316263&doi=10.1002%2fijc.33127&partnerID=40&md5=388debf83ae3d36d9519522dba0ff9echttps://scholars.lib.ntu.edu.tw/handle/123456789/510263We investigated the effects of cigarette smoke extract (CSE) on lung fibroblasts and found that the invasiveness of lung cancer cells was facilitated by the conditioned medium from CSE-treated fibroblasts. CSE induced autophagy in fibroblasts and increased the expression of autophagy-related proteins, including optineurin and Ras-related protein Rab1B. Afterward, the fibroblasts produced high levels of interleukin-8 (IL-8), which promoted cancer cell invasion. The inhibition of either optineurin or Rab1B abrogated a rise in microtubule-associated protein 1 light chain 3 β and a decrease in p62 protein, as well as the production of IL-8, in CSE-treated fibroblasts. A three-dimensional invasion assay using cancer cell spheroids revealed that the invasion of cancer cells alone and the fibroblast-led cancer cell invasion were both enhanced by the conditioned media from CSE-treated fibroblasts. These results suggest that cigarette smoke may induce autophagy and IL-8 secretion in lung fibroblasts and modify the microenvironment to favor invasion of lung cancer cells. ? 2020 UICC[SDGs]SDG3cigarette smoke; guanine nucleotide binding protein; interleukin 8; microtubule associated protein; microtubule associated protein 1 light chain 3beta; optineurin; Rab1B protein; sequestosome 1; unclassified drug; carrier protein; cell cycle protein; CXCL8 protein, human; interleukin 8; OPTN protein, human; Rab protein; Rab1B protein, human; Article; autophagy (cellular); controlled study; cytokine production; cytokine release; human; human cell; lung fibroblast; non small cell lung cancer; priority journal; protein expression; tumor invasion; tumor spheroid; adverse event; autophagy; cancer associated fibroblast; cell motion; conditioned medium; cytology; drug effect; gene knockdown; genetics; immunology; lung; lung tumor; metabolism; multicellular spheroid; non small cell lung cancer; pathology; smoke; smoking; tobacco; tumor cell line; tumor invasion; tumor microenvironment; Autophagy; Cancer-Associated Fibroblasts; Carcinoma, Non-Small-Cell Lung; Cell Cycle Proteins; Cell Line, Tumor; Cell Movement; Culture Media, Conditioned; Gene Knockdown Techniques; Humans; Interleukin-8; Lung; Lung Neoplasms; Membrane Transport Proteins; Neoplasm Invasiveness; rab1 GTP-Binding Proteins; Smoke; Smoking; Spheroids, Cellular; Tobacco; Tumor Microenvironmentjournal article10.1002/ijc.33127324888752-s2.0-85087316263