| RRC ID |
61915
|
| 著者 |
Kajiwara C, Fumoto K, Kimura H, Nojima S, Asano K, Odagiri K, Yamasaki M, Hikita H, Takehara T, Doki Y, Morii E, Kikuchi A.
|
| タイトル |
p63-Dependent Dickkopf3 Expression Promotes Esophageal Cancer Cell Proliferation via CKAP4.
|
| ジャーナル |
Cancer Res
|
| Abstract |
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.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.
|
| 巻・号 |
78(21)
|
| ページ |
6107-6120
|
| 公開日 |
2018-11-1
|
| DOI |
10.1158/0008-5472.CAN-18-1749
|
| PII |
0008-5472.CAN-18-1749
|
| PMID |
30181180
|
| MeSH |
A549 Cells
Adaptor Proteins, Signal Transducing
Adult
Aged
Aged, 80 and over
Animals
Caco-2 Cells
Carcinogenesis
Cell Line, Tumor
Cell Proliferation
Chemokines
Dogs
Esophageal Neoplasms / metabolism*
Esophageal Squamous Cell Carcinoma / metabolism*
Female
Gene Expression Regulation, Neoplastic*
Genes, Reporter
HCT116 Cells
HEK293 Cells
Hep G2 Cells
Humans
Intercellular Signaling Peptides and Proteins / metabolism*
Madin Darby Canine Kidney Cells
Male
Membrane Proteins / metabolism*
Mice
Mice, Inbred BALB C
Mice, Knockout
Middle Aged
Neoplasm Transplantation
Transcription Factors / metabolism*
Tumor Suppressor Proteins / metabolism*
|
| IF |
9.727
|
| リソース情報 |
| ヒト・動物細胞 |
TE-1(RCB1894)
TE-4(RCB2097)
TE-5(RCB1949)
TE-6(RCB1950)
TE-8(RCB2098)
TE-9(RCB1988)
TE-10(RCB2099)
TE-11(RCB2100)
TE-14(RCB2101) |
