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Published on: April 7, 2017
Rab5a is overexpressed in oral cancer and promotes invasion through ERK/MMP signaling
Di Zhang1, Changlong Lu2, Hongjun Ai1
1School of Stomatology, China Medical University, Shenyang 110002, P.R. China.
Abstract:
Ras-related protein Rab-5A (Rab5a) has been identified to be overexpressed in several types of human cancer. However, its clinical significance and biological roles in oral cancer remain unclear. In the present study, the protein expression of Rab5a was examined in 79 cases of oral squamous cell carcinoma samples using immunohistochemistry. It was demonstrated that Rab5a protein was upregulated in 49.3% (39/79) of cancer samples. Small interfering RNA knockdown was performed on Detroit 562 cells with high endogenous expression. Rab5a transfection was performed in FaDu cells with low endogenous levels. Rab5a depletion was revealed to inhibit cell growth, invasion and colony formation while its overexpression facilitated cell growth, invasion, and colony formation. In addition, Rab5a facilitated cell cycle progression and cell migration. It was also demonstrated that Rab5a depletion downregulated and its overexpression upregulated the expression levels of various cell cycle‑associated proteins, and matrix metalloproteinase‑2 (MMP‑2). Furthermore, Rab5a positively regulated the extracellular signal‑regulated kinase (ERK) signaling pathway and promoted epithelial‑mesenchymal transition (EMT). ERK inhibitor PD98059 partially inhibited the role of Rab5a on MMP‑2, cyclin D1, cell proliferation and invasion. The results of the present study suggest that Rab5a is overexpressed in oral cancer tissue samples and promotes the malignant phenotype through EMT and the ERK/MMP‑2 signaling pathway.
Insights
Ras-related protein Rab-5A (Rab5a) is overexpressed in oral cancer, promoting malignant behaviors like growth and invasion. Its inhibition hinders cancer progression, suggesting Rab5a as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Ras-related protein Rab-5A (Rab5a) is implicated in various human cancers.
- The specific role and clinical significance of Rab5a in oral cancer are not well understood.
Purpose of the Study:
- To investigate the expression and functional role of Rab5a in oral squamous cell carcinoma.
- To elucidate the underlying molecular mechanisms, including signaling pathways and epithelial-mesenchymal transition (EMT).
Main Methods:
- Immunohistochemistry was used to assess Rab5a protein expression in 79 oral cancer samples.
- In vitro experiments involved Rab5a knockdown (siRNA) and overexpression (transfection) in oral cancer cell lines (Detroit 562 and FaDu).
- Cell proliferation, invasion, colony formation, cell cycle, migration, and signaling pathway analysis (ERK, MMP-2) were performed.
Main Results:
- Rab5a protein was upregulated in 49.3% of oral cancer samples.
- Rab5a depletion inhibited cell growth, invasion, and colony formation, while overexpression promoted these processes.
- Rab5a facilitated cell cycle progression, migration, and upregulated cell cycle-associated proteins and matrix metalloproteinase-2 (MMP-2).
- Rab5a positively regulated the extracellular signal-regulated kinase (ERK) pathway and promoted EMT. The ERK inhibitor PD98059 partially reversed Rab5a's effects.
Conclusions:
- Rab5a is overexpressed in oral cancer and contributes to the malignant phenotype.
- Rab5a promotes oral cancer progression via EMT and the ERK/MMP-2 signaling pathway.
- Rab5a represents a potential therapeutic target for oral cancer treatment.
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