1. Academic Validation
  2. Helicobacter pylori infection induces POU5F1 upregulation and SPP1 activation to promote chemoresistance and T cell inactivation in gastric cancer cells

Helicobacter pylori infection induces POU5F1 upregulation and SPP1 activation to promote chemoresistance and T cell inactivation in gastric cancer cells

  • Biochem Pharmacol. 2024 May 1:225:116253. doi: 10.1016/j.bcp.2024.116253.
Hanyi Song 1 Xinjie Yao 1 Yuqi Zheng 2 Long Zhou 3
Affiliations

Affiliations

  • 1 Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, PR China.
  • 2 Department of Gastroenterology, Panjin Central Hospital, Panjin 124010, Liaoning, PR China.
  • 3 Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, PR China. Electronic address: zhoulong@cmu.edu.cn.
Abstract

Infection with Helicobacter pylori (H. pylori or Hp) is associated with an increased susceptibility to gastric diseases, notably gastric Cancer (GC). This study investigates the impact of Hp Infection on chemoresistance and immune activity in GC cells. Hp Infection in AGS and MKN-74 cells promoted proliferation, migration and invasion, Apoptosis resistance, and tumorigenic activity of cells under cisplatin (DDP) plus gemcitabine (GEM) treatment. Additionally, it dampened activity of the co-cultured CD8+ T cells. Hp Infection increased POU class 5 homeobox 1 (POU5F1) level, which further activated secreted phosphoprotein 1 (SPP1) transcription to increase its expression. Silencing of either SPP1 or POU5F1 enhanced the GEM sensitivity in GC cells, and it increased the populations of CD8+ T cells and the secretion of immune-active cytokines both in vitro and in xenograft tumors in immunocompetent mice. However, the effects of POU5F1 silencing were counteracted by SPP1 overexpression. Furthermore, the POU5F1/SPP1 axis activated the PI3K/Akt signaling pathway. This study demonstrates that Hp Infection induces POU5F1 upregulation and SPP1 activation, leading to increased DDP/GEM resistance and T cell inactivation in GC cells.

Keywords

Gastric cancer; Gemcitabine resistance; Helicobacter pylori infection; POU5F1; T cell activity.

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