p63-Dependent Dickkopf3 Expression Promotes Esophageal Cancer Cell Proliferation via CKAP4

DOI PDF PubMed 被引用文献11件 参考文献45件
  • Chihiro Kajiwara
    1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Katsumi Fumoto
    1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Hirokazu Kimura
    1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Satoshi Nojima
    2Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Keita Asano
    1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Kazuki Odagiri
    3Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Makoto Yamasaki
    3Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Hayato Hikita
    4Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Tetsuo Takehara
    4Department of Gastroenterology and Hepatology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Yuichiro Doki
    3Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Eiichi Morii
    2Department of Pathology, Graduate School of Medicine, Osaka University, Suita, Japan.
  • Akira Kikuchi
    1Department of Molecular Biology and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Japan.

書誌事項

公開日
2018-11-01
資源種別
journal article
DOI
  • 10.1158/0008-5472.can-18-1749
公開者
American Association for Cancer Research (AACR)

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説明

<jats:title>Abstract</jats:title> <jats:p>Dickkopf3 (DKK3) is a secretory protein that belongs to the DKK family, but exhibits structural divergence from other family members, and its corresponding receptors remain to be identified. Although DKK3 has been shown to have oncogenic functions in certain cancer types, the underlying mechanism by which DKK3 promotes tumorigenesis remains to be clarified. We show here that DKK3 stimulates esophageal cancer cell proliferation via cytoskeleton-associated protein 4 (CKAP4), which acts as a receptor for DKK3. DKK3 was expressed in approximately 50% of tumor lesions of esophageal squamous cell carcinoma (ESCC) cases; simultaneous expression of DKK3 and CKAP4 was associated with poor prognosis. Anti-CKAP4 antibody inhibited both binding of DKK3 to CKAP4 and xenograft tumor formation induced by ESCC cells. p63, a p53-related transcriptional factor frequently amplified in ESCC, bound to the upstream region of the DKK3 gene. Knockdown of p63 decreased DKK3 expression in ESCC cells, and reexpression of DKK3 partially rescued cell proliferation in p63-depleted ESCC cells. Expression of ΔNp63α and DKK3 increased the size of tumor-like esophageal organoids, and anti-CKAP4 antibody inhibited growth of esophageal organoids. Taken together, these results suggest that the DKK3-CKAP4 axis might serve as a novel molecular target for ESCC.</jats:p> <jats:p>Significance: In esophageal cancer, findings identify DKK3 as a poor prognostic indicator and demonstrate CKAP4 inhibition as an effective therapeutic strategy. Cancer Res; 78(21); 6107–20. ©2018 AACR.</jats:p>

収録刊行物

  • Cancer Research

    Cancer Research 78 (21), 6107-6120, 2018-11-01

    American Association for Cancer Research (AACR)

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