EHF suppresses cancer progression by inhibiting ETS1-mediated ZEB expression

ETS homologous factor (EHF) belongs to the epithelium-specific subfamily of the E26 transformation-specific (ETS) transcription factor family. Currently, little is known about EHF’s function in cancer. We previously reported that ETS1 induces expression of the ZEB family proteins ZEB1/δEF1 and ZEB2/...

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Veröffentlicht in:Oncogenesis (New York, NY) NY), 2021-03, Vol.10 (3), p.26-26, Article 26
Hauptverfasser: Sakamoto, Kaname, Endo, Kaori, Sakamoto, Kei, Kayamori, Kou, Ehata, Shogo, Ichikawa, Jiro, Ando, Takashi, Nakamura, Ryosuke, Kimura, Yujiro, Yoshizawa, Kunio, Masuyama, Keisuke, Kawataki, Tomoyuki, Miyake, Kunio, Ishii, Hiroki, Kawasaki, Tomonori, Miyazawa, Keiji, Saitoh, Masao
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Sprache:eng
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Zusammenfassung:ETS homologous factor (EHF) belongs to the epithelium-specific subfamily of the E26 transformation-specific (ETS) transcription factor family. Currently, little is known about EHF’s function in cancer. We previously reported that ETS1 induces expression of the ZEB family proteins ZEB1/δEF1 and ZEB2/SIP1, which are key regulators of the epithelial–mesenchymal transition (EMT), by activating the ZEB1 promoters. We have found that EHF gene produces two transcript variants, namely a long form variant that includes exon 1 (EHF-LF) and a short form variant that excludes exon 1 (EHF-SF). Only EHF-SF abrogates ETS1-mediated activation of the ZEB1 promoter by promoting degradation of ETS1 proteins, thereby inhibiting the EMT phenotypes of cancer cells. Most importantly, we identified a novel point mutation within the conserved ETS domain of EHF , and found that EHF mutations abolish its original function while causing the EHF protein to act as a potential dominant negative, thereby enhancing metastasis in vivo. Therefore, we suggest that EHF acts as an anti-EMT factor by inhibiting the expression of ZEBs, and that EHF mutations exacerbate cancer progression.
ISSN:2157-9024
2157-9024
DOI:10.1038/s41389-021-00313-2