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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
Published on: September 19, 2018
Tyrosine kinase LYN is an oncotarget in human cervical cancer: A quantitative proteomic based study
Shuaibin Liu1, Xiaoming Hao1, Xiaolan Ouyang1
1Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, PR China.
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.
Insights
The study identifies LYN tyrosine kinase as a key oncogenic driver in cervical cancer. Inhibiting LYN shows potential for new therapeutic strategies against this common women's cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Cervical cancer remains a significant global health challenge with complex underlying mechanisms.
- Understanding novel protein profiles is crucial for identifying new therapeutic targets.
Purpose of the Study:
- To identify novel proteins involved in cervical cancer oncogenesis using iTRAQ.
- To investigate the role and mechanism of the identified protein LYN in cervical cancer progression.
Main Methods:
- iTRAQ proteomics to identify differentially expressed proteins in cervical cancer.
- Western blot and immunohistochemistry for protein validation and expression analysis.
- In vitro cell assays (proliferation, migration, invasion) and in vivo tumor growth studies.
Main Results:
- 3300 proteins were found to be aberrantly expressed; LYN tyrosine kinase was selected for further study.
- LYN expression was significantly elevated in cervical cancer tissues and correlated with poor differentiation and advanced FIGO stage.
- LYN inhibition suppressed cancer cell proliferation, migration, and invasion, while LYN overexpression promoted these processes.
- LYN was found to activate the IL-6/STAT3 pathway, facilitating cervical cancer metastasis.
- In vivo studies confirmed that LYN overexpression promotes tumor growth, and LYN knockdown inhibits it.
Conclusions:
- LYN tyrosine kinase acts as an oncogenic gene in cervical cancer.
- LYN is a potential novel therapeutic target for cervical cancer treatment and research.
