title: Inhibition of SRC family kinases reduces myeloid-derived suppressor cells in head and neck cancer.
abstract: SRC family kinases (SFKs), a group of nonreceptor tyrosine kinases, modulate multiple cellular functions, such as cell proliferation, differentiation and metabolism. SFKs display aberrant activity in progressive stages of human cancers. However, the precise role of SFKs in the head and neck squamous cell carcinoma (HNSCC) signaling network is far from clear. In this study, we found that the inhibition of SFKs activity by dasatinib effectively reduced the tumor size and population of MDSCs in the HNSCC mouse model. Molecular analysis indicates that phosphorylation of LYN, rather than SRC, was inhibited by dasatinib treatment. Next, we analyzed LYN expression by immunostaining and found that it was overexpressed in the human HNSCC specimens. Moreover, LYN expression in stromal cells positively correlated with myeloid-derived suppressor cells (MDSCs) makers CD11b and CD33 in human HNSCC. The dual positive expression of LYN in epithelial and stromal cells (EPI+SRT+) was associated with unfavorable overall survival of HNSCC patients. These findings indicate that SFKs may be a potential target for an effective immunotherapy of HNSCC by decreasing MDSCs and moreover, LYN will have an impact on such therapeutic strategy.
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Liang
authors: L
authors: Mao
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Wei-Wei
authors: WW
authors: Deng
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Guang-Tao
authors: GT
authors: Yu
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Lin-Lin
authors: LL
authors: Bu
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Jian-Feng
authors: JF
authors: Liu
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Si-Rui
authors: SR
authors: Ma
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Lei
authors: L
authors: Wu
authors: Functional Genomics Section, Laboratory of Cell and Developmental Biology, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD.
authors: Ashok B
authors: AB
authors: Kulkarni
authors: Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Wen-Feng
authors: WF
authors: Zhang
authors: The State Key Laboratory Breeding Base of Basic Science of Stomatology & Key Laboratory of Oral Biomedicine, Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, China.|Department of Oral Maxillofacial-Head Neck Oncology, School and Hospital of Stomatology, Wuhan University, Wuhan, China.
authors: Zhi-Jun
authors: ZJ
authors: Sun
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D000069439:Dasatinib / Q000494:pharmacology / Q000627:therapeutic use*; D004790:Enzyme Induction / Q000187:drug effects; D004847:Epithelial Cells / Q000201:enzymology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000276:immunology / Q000473:pathology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D058990:Molecular Targeted Therapy; D000072737:Myeloid-Derived Suppressor Cells / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000172:deficiency; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000172:deficiency; D017154:Stromal Cells / Q000201:enzymology; D019139:Tumor Escape; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D018125:Receptors, Transforming Growth Factor beta; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D000069439:Dasatinib
keywords: LYN kinase; SRC family kinase; head and neck cancer; myeloid-derived suppressor cell