Radiation Resistance in KRAS-Mutated Lung Cancer Is Enabled by Stem-like Properties Mediated by an Osteopontin-EGFR Pathway.
作者： Meng Wang , Jing Han , Lynnette Marcar , Josh Black , Qi Liu
DOI: 10.1158/0008-5472.CAN-16-0808
关键词:
摘要: Lung cancers with activating KRAS mutations are characterized by treatment resistance and poor prognosis. In particular, the basis for their to radiation therapy is poorly understood. Here, we describe a phenotype conferred stem-like subpopulation mitosis-like condensed chromatin (MLCC), high CD133 expression, invasive potential, tumor-initiating properties. Mechanistic investigations defined pathway involving osteopontin EGFR in promoting this phenotype. Osteopontin/EGFR-dependent MLCC protected cells against radiation-induced DNA double-strand breaks repressed putative negative regulators of properties, such as CRMP1 BIM. The MLCC-positive subset KRAS-mutated lung that were enriched co-occurring genomic alterations TP53 CDKN2A. Our results illuminate cancers, possible implications prognostic therapeutic strategies. Cancer Res; 77(8); 2018-28. ©2017 AACR.
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