Identification of the KAI1 metastasis suppressor gene as a hypoxia target gene

Biochemical and Biophysical Research Communications
Bogyou KimSung Hee Baek

Abstract

KAI1 is a metastasis suppressor gene known to inhibit cancer metastasis without affecting primary tumorigenicity. Although KAI1 expression has been reported to undergo transcriptional regulation, how its expression is up- or down-regulated by specific upstream signaling pathways has not been studied in detail. In this study, we characterized the regulatory elements within the 500bp upstream region of mouse KAI1 gene and identified a functional hypoxia-response element (HRE) within the promoter region. Hypoxia-dependent induction of KAI1 was directly mediated by hypoxia-inducible factor (HIF)-1alpha binding on the promoter, which subsequently caused increased recruitment of RNA polymerase II for transcriptional activation. The failure of HIF-1alpha recruitment to the KAI1 promoter was observed in Hif-1alpha knockout mouse embryonic fibroblasts. Furthermore, KAI1 protein synthesis was markedly increased in ischemic tissues, suggesting that KAI1 is a hypoxia target gene in vivo.

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Citations

Aug 31, 2011·FEBS Letters·Yien Che Tsai, Allan M Weissman
Sep 4, 2015·Cancer Metastasis Reviews·Jin FengXin A Zhang
Sep 10, 2014·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·C Y WuH Y Li
Jun 3, 2014·Archives of Plastic Surgery·Moon Kyun ChoSang-Han Lee
Dec 12, 2020·Journal of Translational Medicine·Reza JafariJafar Rezaie
Jun 15, 2021·Saudi Journal of Biological Sciences·Khulood M Al-KhaterSuriya Rehman
Sep 18, 2021·Journal of Hematology & Oncology·Jin-Woo LeeHyo-Soo Kim

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