Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine β-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin–eosin staining was used to detect lung metastasis. Liquid chromatography–mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated -sulfur pathway lowered Met‘s inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the -sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR.

中文翻译：

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KLF10/CBS通过促进硫转移途径增加胃癌细胞对蛋氨酸限制的敏感性

胃癌转移是预后不良的主要原因。我们之前的研究表明，蛋氨酸限制（MR）可降低胃癌的侵袭性和运动性。在本研究中，我们研究了MR对胃癌转移的特殊机制。在体外，胃癌细胞（AGS、SNU-5、MKN7、KATO III、SNU-1 和 MKN45）在 MR 培养基中生长 24 小时。在体内，BALB/c 小鼠接受不含蛋氨酸 (Met) 的饮食。 Transwell 实验用于研究细胞侵袭和迁移。使用定量实时 PCR 和蛋白质印迹测定 Krüppel 样因子 10 (KLF10) 和胱硫醚 β-合酶 (CBS) 的量。为了确定 KLF10 和 CBS 之间的关系，使用了染色质免疫沉淀和双荧光素酶报告实验。苏木精-伊红染色用于检测肺转移。采用液相色谱-质谱法测定胱硫醚含量。 MR治疗对胃癌细胞AGS、SNU-5、MKN7、KATO III、SNU-1和MKN45的侵袭和迁移有不同的影响。 KLF10在AGS细胞中高表达，但在KATO III细胞中低表达。 KLF10提高了MR阻止胃癌细胞侵袭和迁移的能力。此外，KLF10 可能与 CBS 相互作用，促进转录。进一步检测发现，抑制KLF10/CBS介导的硫通路可降低Met对肺转移发展的抑制作用。 KLF10转录激活CBS，加速硫通路，增加胃癌细胞对MR的敏感性。