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Knockdown of CREB3L4 Inhibits Autophagy and Reduces Cisplatin Resistance in Gastric Cancer Cells by Downregulating

Wen-Ke Yin1, Xue-Mei Xie2, Xiao-Yan Song3

  • 1Department of Pathology, Institute of Basic Medicine, North Sichuan Medical College, Nanchong, China.

The Kaohsiung Journal of Medical Sciences
|May 8, 2026
PubMed

Insights

CREB3L4 depletion suppresses autophagy and reduces cisplatin resistance in gastric cancer (GC) by downregulating BAG3. This finding offers a potential therapeutic strategy for overcoming chemoresistance in GC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cisplatin resistance is a significant challenge in gastric cancer (GC) treatment.
  • Autophagy is a key mechanism promoting chemoresistance in GC.
  • The role of the CREB3L4/BAG3 axis in GC cisplatin resistance is not well understood.

Purpose of the Study:

  • To investigate the role of CREB3L4 and BAG3 in cisplatin-resistant GC cells.
  • To elucidate the mechanism by which CREB3L4 influences autophagy and cisplatin resistance.
  • To determine if the CREB3L4/BAG3 pathway impacts GC cell apoptosis and proliferation.

Main Methods:

  • Utilized cisplatin-resistant GC cell lines.
  • Performed CREB3L4 knockdown experiments.
  • Assessed autophagy levels, apoptosis, and cell proliferation.
  • Measured BAG3 expression following CREB3L4 manipulation.

Main Results:

  • CREB3L4 and BAG3 were overexpressed in cisplatin-resistant GC cells.
  • CREB3L4 knockdown decreased BAG3 expression.
  • Silencing CREB3L4 inhibited autophagy and alleviated cisplatin resistance.
  • CREB3L4 depletion promoted apoptosis and inhibited cell proliferation, linked to reduced BAG3.

Conclusions:

  • The CREB3L4/BAG3 axis plays a crucial role in regulating autophagy and cisplatin resistance in GC.
  • Depletion of CREB3L4 suppresses autophagy and reduces cisplatin resistance by downregulating BAG3.
  • Targeting the CREB3L4/BAG3 pathway may offer a novel therapeutic approach for overcoming cisplatin resistance in gastric cancer.
Keywords:
Bcl‐2 associated immortality gene 3 (BAG3)CREB3L4autophagycisplatin resistancegastric cancer

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