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Updated: Oct 8, 2025

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FGD3 binds with HSF4 to suppress p65 expression and inhibit pancreatic cancer progression

Feng Guo1,2, Xiang Cheng3, Boping Jing4

  • 1Department of Pancreatic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Oncogene
|January 3, 2022
PubMed

Insights

FGD3 is downregulated in pancreatic cancer, inhibiting tumor growth and metastasis. Its silencing activates NF-κB signaling via HSF4, revealing a new therapeutic target for pancreatic cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Pancreatic cancer is a highly lethal malignancy characterized by deregulated NF-κB signaling.
  • RelA/p65 expression and localization are key regulators of NF-κB activation in pancreatic cancer.
  • FGD3, a regulator of the actin cytoskeleton, inhibits cancer progression in various cancers, but its role in pancreatic cancer is unclear.

Purpose of the Study:

  • To investigate the role of FGD3 in pancreatic cancer.
  • To elucidate the molecular mechanisms underlying FGD3's function in pancreatic cancer.
  • To identify potential therapeutic targets for pancreatic cancer treatment.

Main Methods:

  • Analysis of FGD3 expression in pancreatic cancer tissues.
  • In vitro and in vivo experiments to assess the effects of FGD3 on cancer cell proliferation, invasion, and metastasis.
  • Investigation of the impact of FGD3 silencing on the NF-κB signaling pathway, including HSF4 translocation and p65 expression.

Main Results:

  • FGD3 expression is significantly downregulated in pancreatic cancer tissues.
  • Low FGD3 expression correlates with unfavorable patient prognosis.
  • FGD3 suppresses pancreatic cancer cell proliferation, invasion, and metastasis.
  • FGD3 silencing leads to NF-κB pathway activation through HSF4 nuclear translocation and increased p65 expression.

Conclusions:

  • FGD3 acts as a tumor suppressor in pancreatic cancer.
  • The novel FGD3/HSF4/p65 signaling axis represents a potential therapeutic target for pancreatic cancer.

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