FXYD5 regulates gastric cancer cell metastasis and drug resistance by EMT modulation

Yuning Mao1,2, Yaohua Hu1, Han Meng1

  • 1Division of Cancer Biology, Laboratory Animal Center, Air Force Medical University, 710032, Xi'an, Shaanxi, China.

Cancer Gene Therapy
|February 21, 2025
PubMed

Insights

Gastric cancer (GC) progression and metastasis are linked to elevated FXYD5 levels. Reducing FXYD5 inhibits GC spread and reverses chemotherapy resistance, identifying it as a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Gastric cancer (GC) is a leading cause of cancer mortality worldwide.
  • Drug resistance, recurrence, and metastasis contribute to high GC mortality rates.
  • Novel therapeutic targets are urgently needed for effective GC treatment.

Purpose of the Study:

  • To identify novel therapeutic targets for gastric cancer (GC).
  • To investigate the role of FXYD domain-containing ion transport regulator 5 (FXYD5) in GC progression and metastasis.
  • To evaluate FXYD5 as a potential target for overcoming chemotherapy resistance in GC.

Main Methods:

  • Establishment of patient-derived xenograft (PDX) models of metastatic gastric cancer via orthotopic transplantation.
  • Differential gene expression analysis between primary and metastatic tumors using PCR-array.
  • In vitro experiments involving FXYD5 knockdown to assess its impact on GC cell invasion, metastasis, proliferation, and drug resistance.

Main Results:

  • Metastatic GC tumors exhibited significantly higher FXYD5 expression compared to primary tumors.
  • Reducing FXYD5 expression suppressed GC cell invasion, metastasis, and proliferation.
  • Silencing FXYD5 reversed resistance to doxorubicin and vincristine by modulating epithelial-mesenchymal transition (EMT) and multidrug resistance protein 2 (MRP2) expression.

Conclusions:

  • FXYD5 plays a crucial role in gastric cancer progression, invasion, and metastasis.
  • FXYD5 is implicated in regulating chemotherapy resistance in GC.
  • FXYD5 represents a promising novel therapeutic target for clinical intervention in gastric cancer.

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