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F. Li
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P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)
- Event: WCLC 2015
- Type: Poster
- Track: Biology, Pathology, and Molecular Testing
- Presentations: 1
- Moderators:
- Coordinates: 9/07/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)
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P1.04-069 - LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-Small Cell Lung Cancer Plasticity and Therapeutic Response (ID 705)
09:30 - 09:30 | Author(s): F. Li
- Abstract
Background:
LKB1 regulates both cell growth and energy metabolism. It remains unclear how LKB1 inactivation coordinates tumor progression with metabolic adaptation in non-small cell lung cancer (NSCLC).
Methods:
Mouse Colony, Mouse Treatment and Tumor Analyses Statistical Analysis Hematoxylin and Eosin (HE) Staining and Immunohistochemistry (IHC) Bioinformatics Analysis Cell Lines and In vitro Assays ShRNA, Plasmids, Lentivirus Production and Infection Analysis of Human Lung ADC and Ad-SCC Specimens Western Blotting Enzymatic Activity Assays and Liquid Chromatography-tandem Mass Spectrometry (LC-MS) Analysis Oil red O Staining Reverse Transcription and Quantitative PCR Analysis
Results:
Here in KRAS/LKB1 (KL) mouse model, we reveal differential reactive oxygen species (ROS) levels in lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC). ROS can modulate ADC-to-SCC transdifferentiation (AST). Further, pentose phosphate pathway deregulation and impaired fatty acid oxidation collectively contribute to the redox imbalance and functionally affect AST. Similar tumor and redox heterogeneity also exist in human NSCLC with LKB1 inactivation. In preclinical trials towards metabolic stress, certain KL ADC can develop drug resistance through squamous transdifferentiation.
Conclusion:
This study uncovers critical redox control of tumor plasticity that may affect therapeutic response in NSCLC.
