Reference - Detail
| RRC ID | 87945 |
|---|---|
| Author | Li F, Han X, Li F, Wang R, Wang H, Gao Y, Wang X, Fang Z, Zhang W, Yao S, Tong X, Wang Y, Feng Y, Sun Y, Li Y, Wong KK, Zhai Q, Chen H, Ji H. |
| Title | LKB1 Inactivation Elicits a Redox Imbalance to Modulate Non-small Cell Lung Cancer Plasticity and Therapeutic Response. |
| Journal | Cancer Cell |
| Abstract |
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). Here in Kras(G12D);Lkb1(lox/lox) (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 toward metabolic stress, certain KL ADC can develop drug resistance through squamous transdifferentiation. This study uncovers critical redox control of tumor plasticity that may affect therapeutic response in NSCLC. |
| Volume | 27(5) |
| Pages | 698-711 |
| Published | 2015-5-11 |
| DOI | 10.1016/j.ccell.2015.04.001 |
| PII | S1535-6108(15)00134-8 |
| PMID | 25936644 |
| PMC | PMC4746728 |
| MeSH | AMP-Activated Protein Kinases Animals Carcinoma, Non-Small-Cell Lung / metabolism* Carcinoma, Non-Small-Cell Lung / pathology Carcinoma, Non-Small-Cell Lung / therapy Cell Differentiation Disease Models, Animal Humans Lung Neoplasms / metabolism* Lung Neoplasms / pathology Lung Neoplasms / therapy Mice Oxidation-Reduction Pentose Phosphate Pathway Protein Serine-Threonine Kinases / antagonists & inhibitors* Protein Serine-Threonine Kinases / genetics Reactive Oxygen Species / metabolism |
| IF | 26.602 |
| Resource | |
| Mice | RBRC02975 |