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DMBT1 suppresses progression of gallbladder carcinoma through PI3K/AKT signaling pathway by targeting PTEN
Shen Sheng1, Wang Jiwen1, Zhang Dexiang2
1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Abstract:
Gallbladder carcinoma (GBC) is a highly lethal malignancy of the gastrointestinal tract. Despite extensive research, the underlying molecular mechanism of GBC remains largely unclear. Deleted in malignant brain tumors 1 (DMBT1) is low-expression during cancer progression and as a potential tumor-suppressor gene in various types of cancer. However, its role in Gallbladder cancer remains poorly understood. Here, we found that DMBT1 was significantly low-expression and deletion of copy number in GBC tissues by qRT-PCR and Western blot. Overexpression of DMBT1 impaired survival, promoted apoptosis in GBC cells in vitro, and inhibited tumor progression in vivo. Further study of underlying mechanisms demonstrated that DMBT1 combined with PTEN which could stabilize PTEN protein, resulting in inhibiting the activation of PI3K/AKT signaling pathway. Our study revealed a new sight of DMBT1 as a tumor-suppressor gene on the PI3K/AKT pathway in GBC, which may be a potential therapeutic target for improving treatment.
Insights
Deleted in malignant brain tumors 1 (DMBT1) acts as a tumor suppressor in gallbladder carcinoma (GBC). Low DMBT1 expression correlates with GBC progression, and its restoration inhibits cancer growth by stabilizing PTEN and blocking the PI3K/AKT pathway.
Area of Science:
- Oncology
- Molecular Biology
- Gastroenterology
Background:
- Gallbladder carcinoma (GBC) is a lethal malignancy with unclear molecular mechanisms.
- Deleted in malignant brain tumors 1 (DMBT1) is a potential tumor suppressor, but its role in GBC is poorly understood.
Purpose of the Study:
- To investigate the role of DMBT1 in gallbladder carcinoma.
- To elucidate the molecular mechanisms underlying DMBT1's function in GBC.
Main Methods:
- Quantitative real-time PCR (qRT-PCR) and Western blot analysis to assess DMBT1 expression and copy number.
- In vitro cell culture experiments to evaluate the effects of DMBT1 overexpression on GBC cell survival and apoptosis.
- In vivo studies to assess tumor progression.
- Mechanism studies involving PTEN protein stabilization and PI3K/AKT signaling pathway analysis.
Main Results:
- DMBT1 expression and copy number were significantly reduced in GBC tissues.
- Overexpression of DMBT1 inhibited GBC cell survival and promoted apoptosis in vitro.
- DMBT1 overexpression suppressed tumor progression in vivo.
- DMBT1 stabilizes PTEN protein, leading to the inhibition of the PI3K/AKT signaling pathway.
Conclusions:
- DMBT1 functions as a tumor suppressor in gallbladder carcinoma.
- The tumor-suppressive role of DMBT1 is mediated through the PI3K/AKT pathway via PTEN stabilization.
- DMBT1 represents a potential therapeutic target for GBC treatment.
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