Targeting positive feedback between BASP1 and EGFR as a therapeutic strategy for lung cancer progression
| Autor: | Wei-Chung Cheng, Yuh Pyng Sher, Chia-Chien Lo, Guan-Chin Tseng, Yu-Kai Huang, Ching Chan Lin, Jin-Yuan Shih, Ting-Ting Kuo, K. S. Clifford Chao, Jennifer L. Hsu, Tzu-Hung Hsiao, Liang-Chuan Lai, Xian Sun, Mien Chie Hung, Chia-Fong Cho, Pei-Chih Lee, Yu-Huei Liu, Yu Sen Lin, Wei Chao Chang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Lung Neoplasms BASP1 Medicine (miscellaneous) Kaplan-Meier Estimate combination therapy Mice 0302 clinical medicine Arsenic Trioxide Antineoplastic Combined Chemotherapy Protocols Medicine EGFR-TKI acquired resistance Pharmacology Toxicology and Pharmaceutics (miscellaneous) Lung EGFR inhibitors Feedback Physiological Brain Neoplasms Brain Prognosis ErbB Receptors 030220 oncology & carcinogenesis Gene Knockdown Techniques Adenocarcinoma Tyrosine kinase Research Paper Signal Transduction Brain Acid Soluble Protein 1 Adenocarcinoma of Lung Nerve Tissue Proteins 03 medical and health sciences Cell Line Tumor Animals Humans Lung cancer Protein Kinase Inhibitors business.industry Gene Expression Profiling Cell Membrane Membrane Proteins medicine.disease lung adenocarcinoma Xenograft Model Antitumor Assays Repressor Proteins 030104 developmental biology Membrane protein Tumor progression Drug Resistance Neoplasm Tissue Array Analysis Mutation Proteolysis Cancer research business Brain metastasis |
| Zdroj: | Theranostics |
| ISSN: | 1838-7640 |
| Popis: | Rationale: Brain metastasis in patients with lung cancer is life-threatening. However, the molecular mechanism for this catastrophic disease remains elusive, and few druggable targets are available. Therefore, this study aimed to identify and characterize proteins that could be used as therapeutic targets. Methods: Proteomic analyses were conducted to identify differentially expressed membrane proteins between brain metastatic lung cancer cells and primary lung cancer cells. A neuronal growth-associated protein, brain acid soluble protein 1 (BASP1), was chosen for further investigation. The clinical relevance of BASP1 in lung adenocarcinoma was first assessed. Tyrosine kinase activity assays and in vitro and in vivo functional assays were conducted to explore the oncogenic mechanisms of BASP1. Results: The protein levels of BASP1 were positively associated with tumor progression and poor prognosis in patients with lung adenocarcinoma. Membrane-bound BASP1 increased EGFR signaling and stabilized EGFR proteins by facilitating their escape from the ubiquitin-proteasome pathway. Reciprocally, activation of EGFR recruited more BASP1 to the plasma membrane, generating a positive feedback loop between BASP1 and EGFR. Moreover, the synergistic therapeutic effects of EGFR tyrosine kinase inhibitor and arsenic trioxide led to a reduction in the level of BASP1 protein observed in lung cancer cells with acquired resistance to EGFR inhibitors. Conclusions: The reciprocal interaction between BASP1 and EGFR facilitates EGFR signaling in brain metastatic lung cancer. Targeting the newly identified BASP1-EGFR interaction could open new venues for lung cancer treatment. |
| Databáze: | OpenAIRE |
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