Helicobacter pylori promotes epithelial-to-mesenchymal transition by downregulating CK2β in gastric cancer cells

So Dam Lee, Haengdueng Jeong, Bo Ram Hwang, Byeong Min Yu, Yejin Cho, Ki Teak Nam, Hyunki Kim, Yong Chan Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Strains of Helicobacter pylori that are positive for the oncoprotein CagA (cytotoxin-associated gene A) are associated with gastric cancer and might be related to the epithelial-to-mesenchymal transition (EMT). Casein kinase 2 (CK2) is a serine/threonine protein kinase that plays a major role in tumorigenesis through signaling pathways related to the EMT. However, the role played by the interaction between CagA and CK2 in gastric carcinogenesis is poorly understood. Although CK2α protein expression remained unchanged during H. pylori infection, we found that CK2α kinase activity was increased in gastric epithelial cells. We also found that the CK2β protein level decreased in H. pylori-infected gastric cancer cells in CagA-dependent manner and demonstrated that CagA induced CK2β degradation via HDM2 (human double minute 2; its murine equivalent is MDM2). We observed that CagA induced HDM2 protein phosphorylation and that p53 levels were decreased in H. pylori-infected gastric cancer cells. In addition, downregulation of CK2β induced AKT Ser473 phosphorylation and decreased the AKT Ser129 phosphorylation level in gastric cancer cells. We also found that the downregulation of CK2β triggered the upregulation of Snail levels in gastric cancer cells. Furthermore, our in vivo experiments and functional assays of migration and colony formation suggest that CK2β downregulation is a major factor responsible for the EMT in gastric cancer. Therefore, CK2 could be a key mediator of the EMT in H. pylori-infected gastric cancer and could serve as a molecular target for gastric cancer treatment.

Original languageEnglish
Article number166588
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1869
Issue number1
DOIs
Publication statusPublished - 2023 Jan 1

Bibliographical note

Publisher Copyright:
© 2022 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology

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