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.

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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