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LYN expression predicts the response to dasatinib in a subpopulation of lung adenocarcinoma patients
- Source :
- Oncotarget
- Publication Year :
- 2016
- Publisher :
- Impact Journals, LLC, 2016.
-
Abstract
- // Yu Jin Kim 1 , Sungyoul Hong 2 , Minjung Sung 1 , Min Jeong Park 2 , Kyungsoo Jung 1, 3 , Ka-Won Noh 1, 3 , Doo-Yi Oh 1, 3 , Mi-Sook Lee 1, 3 , Ensel Oh 1, 3 , Young Kee Shin 2, 4 , Yoon-La Choi 1, 3, 5 1 Laboratory of Cancer Genomics and Molecular Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 Laboratory of Molecular Pathology and Cancer Genomics, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea 3 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, Korea 4 The Center for Anti-cancer Companion Diagnostics, Bio-MAX/N-Bio, Seoul National University, Seoul, Korea 5 Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea Correspondence to: Yoon-La Choi, email: ylachoi@skku.edu Young Kee Shin, email: ykeeshin@snu.ac.kr Keywords: LYN, dasatinib, lung adenocarcinoma subgroup, SRC, YES Received: March 16, 2016 Accepted: October 01, 2016 Published: October 14, 2016 ABSTRACT Therapies targeting SRC family kinases (SFKs) have shown efficacy in treating non-small cell lung cancer (NSCLC). However, recent clinical trials have found that the SFK inhibitor dasatinib is ineffective in some patient cohorts. Regardless, dasatinib treatment may benefit some NSCLC patient subgroups. Here, we investigated whether expression of LYN, a member of the SFK family, is associated with patient survival, the efficacy of dasatinib, and/or NSCLC cell viability. LYN expression was associated with poor overall survival in a multivariate analysis, and this association was strongest in non-smoker female patients with adenocarcinoma (ADC). In lung ADC cells, LYN expression enhanced cell proliferation, migration, and invasion. Dasatinib inhibited LYN activity and decreased cell viability in LYN-positive ADC cell lines and xenografts. Additionally, we identified the SFKs SRC and YES as candidate dasatinib targets in LYN-negative ADC cell lines. Our findings suggest that LYN is a useful prognostic marker and a selective target of dasatinib therapy in the lung ADC subpopulation especially in female non-smokers with lung ADC.
- Subjects :
- Male
0301 basic medicine
Oncology
Lung Neoplasms
Time Factors
Dasatinib
Kaplan-Meier Estimate
0302 clinical medicine
Cell Movement
Risk Factors
Carcinoma, Non-Small-Cell Lung
hemic and lymphatic diseases
Aged, 80 and over
Molecular pathology
Smoking
hemic and immune systems
Middle Aged
Treatment Outcome
src-Family Kinases
030220 oncology & carcinogenesis
Adenocarcinoma
Female
YES
Research Paper
SRC
Proto-oncogene tyrosine-protein kinase Src
medicine.drug
Adult
medicine.medical_specialty
Cell Survival
Adenocarcinoma of Lung
Antineoplastic Agents
Young Adult
03 medical and health sciences
Sex Factors
LYN
Cell Line, Tumor
Internal medicine
Biomarkers, Tumor
medicine
Humans
Neoplasm Invasiveness
Protein Kinase Inhibitors
Aged
Cell Proliferation
Proportional Hazards Models
business.industry
Cancer
lung adenocarcinoma subgroup
medicine.disease
Xenograft Model Antitumor Assays
respiratory tract diseases
body regions
Clinical trial
030104 developmental biology
Multivariate Analysis
Immunology
business
Biomedical sciences
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....0ad0b0fba67500bd6e78c0d45b34b6d1