Tyrosine kinase LYN is an oncotarget in human cervical cancer: A quantitative proteomic based study

Oncotarget. 2016 Nov 15;7(46):75468-75481. doi: 10.18632/oncotarget.12258.

Abstract

Cervical cancer is one of the most common malignant tumor in women. The mechanisms of cervical cancer are intricate and have not been fully understood. Therefore, we employed iTRAQ to obtain novel proteins profile which participates in the tumor oncogenesis of cervical cancer. 3300 proteins were identified aberrantly expressed in cervical cancer, and western bolt was performed to validate the results of iTRAQ. Then, we selected LYN for further study. Immunohistochemistry identified that LYN expression was significantly increased in cervical cancer tissues than that in cancer adjacent normal cervical tissues and normal cervical tissues. The increased LYN expression was significantly correlated with cancer differentiation and FIGO stage. Silencing LYN inhibited cell proliferation, migration and invasion, conversely, overexpression LYN promoted cell proliferation, migration and invasion. In terms of mechanism, LYN could also promote cervical cancer cells metastasis through activating IL-6/STAT3 pathway. In vivo study, overexpression LYN promoted tumor growth, meanwhile knockdown LYN inhibited tumor growth. These results indicate that LYN tyrosine kinase is an oncogenic gene and can serve as a novel target for cervical cancer research and therapy.

Keywords: IL-6; LYN; STAT3; cervical cancer; iTRAQ.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Oncogene Proteins / antagonists & inhibitors
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism*
  • Protein Binding
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Proteome
  • Proteomics / methods
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects
  • Uterine Cervical Neoplasms / genetics
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • src-Family Kinases / antagonists & inhibitors
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Antineoplastic Agents
  • Interleukin-6
  • Oncogene Proteins
  • Protein Kinase Inhibitors
  • Proteome
  • STAT3 Transcription Factor
  • lyn protein-tyrosine kinase
  • src-Family Kinases