2. Academic Validation
  3. Identification of RECK as a protective prognostic indicator and a tumor suppressor through regulation of the ERK/MAPK signaling pathway in gastric cancer

Identification of RECK as a protective prognostic indicator and a tumor suppressor through regulation of the ERK/MAPK signaling pathway in gastric cancer

  • J Transl Med. 2023 Oct 30;21(1):766. doi: 10.1186/s12967-023-04644-z.
Fangyuan Qi 1,  Yaru Wang 1,  Bingxin Yu 2,  Fan Li 3 4 5 6 7
Affiliations

Affiliations

  • 1 The Key Laboratory of Zoonosis, Department of Pathogenobiology, Chinese Ministry of Education, College of Basic Medicine, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China.
  • 2 Department of Ultrasound, The Third Hospital of Jilin University, Changchun, Jilin, People's Republic of China.
  • 3 The Key Laboratory of Zoonosis, Department of Pathogenobiology, Chinese Ministry of Education, College of Basic Medicine, Jilin University, No. 126 Xinmin Street, Changchun, 130021, Jilin, People's Republic of China. lifan@jlu.edu.cn.
  • 4 The Key Laboratory for Bionics Engineering, Ministry of Education, Jilin University, Changchun, People's Republic of China. lifan@jlu.edu.cn.
  • 5 Engineering Research Center for Medical Biomaterials of Jilin Province, Jilin University, Changchun, People's Republic of China. lifan@jlu.edu.cn.
  • 6 Key Laboratory for Health Biomedical Materials of Jilin Province, Jilin University, Changchun, People's Republic of China. lifan@jlu.edu.cn.
  • 7 State Key Laboratory of Pathogenesis, Prevention, and Treatment of High Incidence Diseases in Central Asia, Urumqi, Xinjiang, People's Republic of China. lifan@jlu.edu.cn.
PMID: 37904179 DOI: 10.1186/s12967-023-04644-z
Abstract

Background: Gastric Cancer (GC) ranks as the fifth most common Cancer worldwide and is characterized by its significant heterogeneity and unfavorable prognosis. Thus, identifying efficient prognostic factors and understanding the underlying molecular mechanisms in GC are essential for improving patient outcomes. In this study, we aimed to investigate the role of RECK (reversion-inducing cysteine-rich protein with Kazal motifs) in the prognostic significance and molecular mechanisms of its biological function in GC.

Methods: Multiple bioinformatics strategies were performed to detect the potential functions and prognostic efficiency of RECK in GC. Rescue experiments revealed that the molecular mechanism by which RECK in inhibited tumor proliferation, migration, and invasion was mediated by ERK/MAPK signaling in AGS and HGC-27 cells. Using integrated bioinformatics analysis and western blot assay, we investigated the potential interaction between CALD1 and RECK.

Results: Our findings revealed significantly decreased RECK expression in GC samples compared to normal samples and RECK was identified as a promising predictor for the prognosis of GC patients. Moreover, upregulation of RECK demonstrated a distinctly positive association with a high-immunity and low-metastasis microenvironment in GC. Mechanistically, the antitumour effects of RECK on hampering tumor cell growth, migration, and invasion were mediated by the ERK/MAPK signaling pathway. In addition, we also illustrated that RECK inhibited the phosphorylation of CALD1 mediated by decreased phosphorylation of ERK.

Conclusions: RECK is a promising prognostic biomarker and may shape a high-tumor-immunity and low-metastasis microenvironment in patients with GC. Moreover, RECK exerted its tumor-suppressive effects by the inactivation of ERK/MAPK signaling in GC cells.

Keywords

CALD1; ERK/MAPK; Gastric cancer; RECK; Tumor suppressor.

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