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Updated: Jun 27, 2025

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Fasting-induced RNF152 resensitizes gallbladder cancer cells to gemcitabine by inhibiting mTORC1-mediated glycolysis

Ying Tao1, Zijun Gong2,3,4,5, Sheng Shen2,3,4,5

  • 1Department of General Surgery, Shanghai Xuhui Central Hospital, Zhongshan-Xuhui Hospital, Fudan University, Shanghai, China.

Iscience
|May 6, 2024
PubMed

Insights

RNF152, a protein downregulated in gallbladder cancer, suppresses mTORC1 activity. Upregulating RNF152 enhances gemcitabine sensitivity by inhibiting cancer cell glycolysis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Metabolism

Background:

  • Aberrant mTORC1 signaling, driven by the Ragulator complex, is linked to cancer and drug resistance.
  • Cellular metabolic status is influenced by fasting, which upregulates RNF152.
  • Gallbladder cancer (GBC) exhibits altered metabolism and resistance to therapies like gemcitabine.

Purpose of the Study:

  • To investigate the role of RNF152 in regulating mTORC1 signaling and gemcitabine sensitivity in GBC.
  • To elucidate the mechanism by which RNF152 affects the Ragulator complex and cellular metabolism.

Main Methods:

  • Quantification of RNF152 and p18 protein levels in GBC tissues.
  • Mechanistic studies involving activators, inhibitors, and lentiviral transfections.
  • Assessment of gemcitabine sensitivity, glycolysis, and mTORC1 activity under varying RNF152 expression levels.

Main Results:

  • RNF152 expression is significantly lower in GBC tissues compared to adjacent non-cancerous tissues.
  • RNF152 overexpression enhances gemcitabine sensitivity and suppresses glycolysis in GBC cells.
  • RNF152 targets the Ragulator subunit p18 for ubiquitination and proteasomal degradation, thereby inhibiting mTORC1 activity.

Conclusions:

  • RNF152 acts as a tumor suppressor in GBC by inhibiting mTORC1-driven glycolysis.
  • RNF152 upregulation, potentially induced by fasting, enhances sensitivity to gemcitabine chemotherapy.
  • Targeting RNF152 or modulating mTORC1 signaling may represent therapeutic strategies for GBC.
Keywords:
CancerCell biologyMolecular biology

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