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  6. Klf10/cbs Increases The Sensitivity Of Gastric Carcinoma Cells To Methionine Restriction By Promoting Sulfur Transfer Pathway

KLF10/CBS increases the sensitivity of gastric carcinoma cells to methionine restriction by promoting sulfur transfer pathway

Lin Xin1, Zhi-Yang Liu1, Chen-Xi Liu2

  • 1Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.

Experimental Cell Research
|March 18, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Methionine restriction (MR) impacts gastric cancer metastasis by regulating Krüppel-like factor 10 (KLF10) and cystathionine β-synthase (CBS). KLF10 enhances MR

Area of Science:

  • Oncology
  • Molecular Biology
  • Nutritional Science

Background:

  • Gastric cancer metastasis significantly worsens patient prognosis.
  • Previous studies indicated methionine restriction (MR) reduces gastric carcinoma invasiveness and motility.
  • The precise mechanisms underlying MR's anti-metastatic effects require further elucidation.

Purpose of the Study:

  • To investigate the specific molecular mechanisms by which methionine restriction (MR) influences gastric carcinoma metastasis.
  • To explore the roles of Krüppel-like factor 10 (KLF10) and cystathionine β-synthase (CBS) in MR-mediated anti-metastatic effects.
  • To determine the interaction between KLF10 and CBS and their impact on the trans-sulfur pathway in gastric cancer.

Main Methods:

  • In vitro studies utilized various gastric carcinoma cell lines (AGS, SNU-5, MKN7, KATO III, SNU-1, MKN45) cultured under MR conditions.
Keywords:
CBSGastric cancerKLF10Methionine restriction

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  • In vivo experiments involved BALB/c mice fed a methionine-free (Met-) diet.
  • Cell invasion and migration were assessed using Transwell assays; KLF10 and CBS expression was quantified via qRT-PCR and Western blot; KLF10-CBS interaction was analyzed through ChIP and dual-luciferase assays; lung metastasis was detected by H&E staining; cystathionine levels were measured by LC-MS.
  • Main Results:

    • Methionine restriction (MR) exhibited variable effects on the invasion and migration of different gastric carcinoma cell lines.
    • Krüppel-like factor 10 (KLF10) expression levels varied among cell lines, with high expression in AGS and low expression in KATO III cells.
    • KLF10 significantly enhanced MR's inhibitory effects on gastric carcinoma cell invasion and migration, potentially through transcriptional activation of cystathionine β-synthase (CBS) and acceleration of the trans-sulfur pathway.

    Conclusions:

    • Krüppel-like factor 10 (KLF10) plays a crucial role in mediating the anti-metastatic effects of methionine restriction (MR) in gastric cancer.
    • KLF10 interacts with cystathionine β-synthase (CBS) to regulate the trans-sulfur pathway, influencing gastric carcinoma cell susceptibility to MR.
    • Targeting the KLF10/CBS-mediated trans-sulfur pathway may represent a therapeutic strategy to enhance the efficacy of MR in preventing gastric cancer lung metastasis.
    Sensitivity