Radiation Resistance in KRAS-Mutated Lung Cancer Is Enabled by Stem-like Properties Mediated by an Osteopontin–EGFR Pathway

• Published in: Cancer research (Chicago, Ill.) Vol. 77; no. 8; pp. 2018 - 2028
• Main Authors: Wang, Meng, Han, Jing, Marcar, Lynnette, Black, Josh, Liu, Qi, Li, Xiangyong, Nagulapalli, Kshithija, Sequist, Lecia V., Mak, Raymond H., Benes, Cyril H., Hong, Theodore S., Gurtner, Kristin, Krause, Mechthild, Baumann, Michael, Kang, Jing X., Whetstine, Johnathan R., Willers, Henning
• Format: Journal Article
• Language: English
• Published: United States American Association for Cancer Research, Inc 15.04.2017
• Subjects: A549 Cells; Animals; Cancer therapies; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - radiotherapy; Chromatin; DNA damage; Epidermal growth factor receptors; Female; Genotype & phenotype; Heterografts; Humans; Invasiveness; K-Ras protein; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Lung Neoplasms - radiotherapy; Lungs; Male; Mice; Mice, Nude; Mitosis; Mutation; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neoplastic Stem Cells - radiation effects; Osteopontin; Osteopontin - biosynthesis; Osteopontin - genetics; Osteopontin - metabolism; p53 Protein; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; Radiation Tolerance - genetics; Receptor, Epidermal Growth Factor - metabolism; Signal Transduction; Treatment resistance

Lung cancers with activating KRAS mutations are characterized by treatment resistance and poor prognosis. In particular, the basis for their resistance to radiation therapy is poorly understood. Here, we describe a radiation resistance phenotype conferred by a stem-like subpopulation characterized b...