Hepatic metastasis of gastric cancer is associated with enhanced expression of ethanolamine kinase 2 via the p53–Bcl-2 intrinsic apoptosis pathway

To test the reproducibility of the cell crock assay, we evaluated influences of Ethanolamine kinase 2 KO on cell cycle regulation using the Muse Cell Cycle Kit under the manufacturer’s protocol

Takashi Miwa; Mitsuro Kanda; Dai Shimizu; Shinichi Umeda; Koichi Sawaki; Haruyoshi Tanaka; Chie Tanaka; Norifumi Hattori; Masamichi Hayashi; Suguru Yamada; Goro Nakayama; Masahiko Koike; Yasuhiro Kodera

2021

Scholarcy highlights

  • Gastric cancer with hepatic metastasis has a poor prognosis
  • We decided to focus on Ethanolamine kinase 2 for the following reasons: it showed high specificity for hepatic recurrence indicated by little changes in the peritoneal and nodal recurrence groups, the nucleotide sequence of ETNK2 is available, and there were no previous reports about association between ETNK2 and cancers of the GI tract
  • High ETNK2 expression in GC tissues is associated with hepatic recurrence and poor prognosis To assess the clinical significance of ETNK2 mRNA expression in GC, we first analysed its expression in data sets from institutional cohort, consisting of normal stomach tissues and GC specimens from patients with Stage I, II/III, or IV GC
  • In this study, we conducted pattern-specific transcriptome analysis of GC tissues to identify molecules potentially involved in hepatic metastasis
  • We established stable ETNK2 KO GC cell lines and demonstrated a role for ETNK2 in behaviours associated with metastasis, namely, enhanced proliferation, migration, and invasion and reduced apoptosis
  • Analysis of KM survival curves showed a significant association between high ETNK2 mRNA and significantly shorter overall survival in the full institutional cohort 1.58, 95% confidence intervals
  • We examined ETNK2 expression at the mRNA and protein levels in surgically resected GC specimens and identified significant positive associations between high expression and worse prognosis and hepatic recurrence
  • Subcutaneous tumours formed by both parental MKN1 and Ethanolamine kinase 2 KO cells have no differences in the expression of HIF-1a, which mediates the cellular response to hypoxia as transcriptome factor. Caspase-3 is an effector caspase that is cleaved and activated by initiator caspase

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