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Published on: January 12, 2020
Gab2 plays a carcinogenic role in ovarian cancer by regulating CrkII
1Department of Gynecological Oncology, The Affiliated Tumor Hospital of Nantong University, Nantong Tumor Hospital, Nantong, Jiangsu, China.
Objective:
To detect the expression of Growth factor binding protein 2 associated binding protein 2 (Gab2) and CT10 regulator of kinase II (CrkII) in ovarian cancer and analyze their clinical significance. To explore the effects of Gab2 and CrkII on the biological behavior of ovarian cancer cells. To analyze the possible molecular mechanism of Gab2 in the development of ovarian cancer.
Methods:
Immunohistochemistry was used to detect the expression of Gab2 and CrkII in ovarian cancer. Chi square test was used to analyze the correlation between Gab2, CrkII and clinical parameters. Using Cox regression model to evaluate the risk factors affecting the prognosis. To analyze the correlation between Gab2, CrkII and survival rate by Kaplan-Meier. Cell experiments were preformed to explore the effects of Gab2 and CrkII on the biological behavior of cells. The interaction between Gab2 and CrkII was explored by immunoprecipitation.
Results:
Immunohistochemistry revealed that high expression of Gab2 and CrkII in ovarian cancer. Patients with high expression of Gab2 or CrkII had higher International Federation of Gynecology and Obstetrics (FIGO) stage, grade and platinum-resistance recurrence. Multivariate analysis showed that Gab2 and CrkII were independent prognostic factors. Kaplan-Meier curve showed that the higher Gab2 and CrkII were, the poor prognosis the patients had. We observed that the overexpression of Gab2 and CrkII promoted the proliferation, metastasis and reduced chemosensitivity of cells. Conversely, the knockdown of Gab2 and CrkII resulted in the opposite results. In CrkII-knockdown cells, we found that Gab2 mediates biological behavior through CrkII.
Conclusions:
The expression of Gab2 and CrkII increase in ovarian cancer. The higher expression of Gab2 and CrkII predict the poor prognosis of patients. Gab2 and CrkII promote the proliferation and migration and reduce the chemosensitivity of cells. Gab2 regulates the biological behaviors of ovarian cancer cells through CrkII.
Insights
High expression of Gab2 and CrkII in ovarian cancer correlates with poor prognosis and increased cell proliferation and metastasis. Gab2 influences these behaviors through CrkII, suggesting potential therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Ovarian cancer remains a significant health challenge with complex molecular underpinnings.
- Understanding the roles of specific proteins like Gab2 and CrkII is crucial for identifying novel therapeutic targets and improving patient outcomes.
Purpose of the Study:
- To investigate the expression levels of Gab2 and CrkII in ovarian cancer tissues.
- To analyze the clinical significance of Gab2 and CrkII expression in relation to patient prognosis and disease characteristics.
- To elucidate the functional roles of Gab2 and CrkII in ovarian cancer cell behavior and explore their molecular interplay.
Main Methods:
- Immunohistochemistry was employed to assess Gab2 and CrkII protein expression in ovarian cancer samples.
- Statistical analyses, including Chi-square tests, Cox regression, and Kaplan-Meier survival analysis, were used to evaluate clinical correlations and prognostic value.
- In vitro cell experiments, including overexpression and knockdown studies, were conducted to determine the effects on cell proliferation, migration, and chemosensitivity, with immunoprecipitation used to explore protein interactions.
Main Results:
- Elevated expression of Gab2 and CrkII was observed in ovarian cancer, significantly correlating with advanced FIGO stage, higher grade, and platinum-resistance recurrence.
- Both Gab2 and CrkII were identified as independent prognostic factors, with higher expression linked to poorer patient survival.
- Overexpression of Gab2 and CrkII promoted ovarian cancer cell proliferation and metastasis while reducing chemosensitivity; conversely, knockdown yielded opposite effects, and Gab2 was found to mediate its effects via CrkII.
Conclusions:
- Increased expression of Gab2 and CrkII is a hallmark of ovarian cancer and serves as a predictor of poor prognosis.
- Gab2 and CrkII play critical roles in promoting tumor progression, including enhanced proliferation, migration, and diminished chemosensitivity.
- Gab2 exerts its influence on ovarian cancer cell behavior through its interaction with CrkII, highlighting a key molecular pathway for potential therapeutic intervention.
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