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Critical Reviews™ in Oncogenesis

Publication de 4  numéros par an

ISSN Imprimer: 0893-9675

ISSN En ligne: 2162-6448

SJR: 0.395 SNIP: 0.322 CiteScore™:: 2.5 H-Index: 54

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Role of Raf Kinase Inhibitor Protein in Helicobacter pylori-Mediated Signaling in Gastric Cancer

Volume 19, Numéro 6, 2014, pp. 469-481
DOI: 10.1615/CritRevOncog.2014012044
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RÉSUMÉ

Helicobacter pylori is a helical bacterium that colonizes the stomach in over half of the world's population. Infection with this bacterium has been linked to peptic ulcer disease and gastric cancer. The bacterium has been shown to affect regulatory pathways in its host cells through specific virulence factors that control gene expression. Infection with H. pylori increases levels of phosphorylation of Raf kinase inhibitor protein (pRKIP) in gastric adenocarcinoma (AGS) cells in vitro and in vivo. We investigated the role of H. pylori in the phosphorylation of RKIP as a possible mechanism to downregulate pro-survival signals in gastric adenocarcinoma. pRKIP induces RKIP transcriptional activity, which serves to induce apoptosis of damaged cells to prevent further tumorigenesis. Infection of wild type and RKIP knockout mice with H. pylori for 2 months further confirmed roles of RKIP and pRKIP in the prevention of gastric cancer progression. Loss of RKIP in AGS cells results in increased expression of the Cag A virulence factor after H. pylori infection and RKIP overexpression inhibits H. pylori-mediated STAT3 phosphorylation and STAT3 and NF-κB transcriptional activity. We examined the role of mTOR (mammalian target of rapamycin) after H. pylori infection on the phosphorylation of RKIP. Cells treated with rapamycin, an inhibitor of mTOR, displayed less expression of pRKIP after H. pylori infection. Microarray antibody analysis was conducted on wild-type and RKIP-knockdown AGS cells and showed that in the absence of RKIP, there was increased expression of pro-tumorigenic proteins such as EGFR, Raf-1, and MAPKs. Although further work is needed to confirm the interaction of RKIP and mTOR in AGS cells as a result of H. pylori infection, we hypothesize that H. pylori-mediated induction of pro-survival signaling in gastric epithelial cells induces a feedback response through the activation of RKIP. The phosphorylated, or active, form of RKIP is important in protecting gastric epithelial cells from tumorigenesis after H. pylori infection.

CITÉ PAR
  1. Sgouras Dionyssios N., Trang Tran Thi Huyen, Yamaoka Yoshio, Pathogenesis ofHelicobacter pyloriInfection, Helicobacter, 20, 2015. Crossref

  2. Hong C.‐H., Tu H.‐P., Lin J.‐R., Lee C.‐H., An estimation of the incidence of tuberous sclerosis complex in a nationwide retrospective cohort study (1997–2010), British Journal of Dermatology, 174, 6, 2016. Crossref

  3. Wottrich Stephanie, Kaufhold Samantha, Chrysos Emmanuel, Zoras Odysseas, Baritaki Stavroula, Bonavida Benjamin, Inverse correlation between the metastasis suppressor RKIP and the metastasis inducer YY1: Contrasting roles in the regulation of chemo/immuno-resistance in cancer, Drug Resistance Updates, 30, 2017. Crossref

  4. Wu Wen-Wei, Ye Zi-Jing, Xu Yi-Mou, Zhang Jin, Tang Jin-Sen, Ergosta-7,22-diene-2β,3α,9α-triol (EGDT) from Ganoderma lucidum inhibits nasopharyngeal carcinoma cells by blocking EGFR signaling pathway, Chinese Herbal Medicines, 10, 1, 2018. Crossref

  5. Zaravinos Apostolos, Bonavida Benjamin, Chatzaki Ekaterini, Baritaki Stavroula, RKIP: A Key Regulator in Tumor Metastasis Initiation and Resistance to Apoptosis: Therapeutic Targeting and Impact, Cancers, 10, 9, 2018. Crossref

  6. Noh Hae Sook, Hah Young-Sool, Ha Ji Hye, Kang Min Young, Zada Sahib, Rha Sun Young, Kang Sang Soo, Kim Hyun Joon, Park Jae-Yong, Byun June-Ho, Hahm Jong Ryeal, Shin Jeong Kyu, Jeong Sang-Ho, Lee Young-Joon, Kim Deok Ryong, Regulation of the epithelial to mesenchymal transition and metastasis by Raf kinase inhibitory protein-dependent Notch1 activity, Oncotarget, 7, 4, 2016. Crossref

  7. Rama Martina, Bonavida Benjamin, Identification of regulatory crosstalks between RKIP and BRCA1 tumor suppressors in healthy tissues and cancer (breast and ovarian): Therapeutic implications, in Prognostic and Therapeutic Applications of RKIP in Cancer, 2020. Crossref

  8. Touboul Roni, Baritaki Stavroula, Zaravinos Apostolos, Bonavida Benjamin, RKIP Pleiotropic Activities in Cancer and Inflammatory Diseases: Role in Immunity, Cancers, 13, 24, 2021. Crossref

  9. Hu Chi-Tan, Mandal JayaPrakash, Wu Wen-Sheng, Regulation on tumor metastasis by Raf kinase inhibitory protein: New insight with reactive oxygen species signaling, Tzu Chi Medical Journal, 33, 4, 2021. Crossref

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