High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer

Masakazu Sugiyama, Eiji Oki, Yu Nakaji, Satoshi Tsutsumi, Naomi Ono, Ryota Nakanishi, Masahiko Sugiyama, Yuichiro Nakashima, Hideto Sonoda, Kippei Ohgaki, Nami Yamashita, Hiroshi Saeki, Shinji Okano, Hiroyuki Kitao, Masaru Morita, Yoshinao Oda, Yoshihiko Maehara

研究成果: ジャーナルへの寄稿記事

10 引用 (Scopus)

抄録

The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse-free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E-cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E-cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E-cadherin expression. In vitro studies suggested that RAS-MEK-MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.

元の言語英語
ページ(範囲)1705-1716
ページ数12
ジャーナルCancer Science
107
発行部数11
DOI
出版物ステータス出版済み - 11 1 2016

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Colorectal Neoplasms
Ligands
Cadherins
Epithelial-Mesenchymal Transition
Recurrence
Jagged-1 Protein
MAP Kinase Kinase Kinases
Wnt Signaling Pathway
Gene Silencing
Colonic Neoplasms
Small Interfering RNA
Cell Survival
Carcinogenesis
Multivariate Analysis
Immunohistochemistry
Cell Proliferation
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer. / Sugiyama, Masakazu; Oki, Eiji; Nakaji, Yu; Tsutsumi, Satoshi; Ono, Naomi; Nakanishi, Ryota; Sugiyama, Masahiko; Nakashima, Yuichiro; Sonoda, Hideto; Ohgaki, Kippei; Yamashita, Nami; Saeki, Hiroshi; Okano, Shinji; Kitao, Hiroyuki; Morita, Masaru; Oda, Yoshinao; Maehara, Yoshihiko.

:: Cancer Science, 巻 107, 番号 11, 01.11.2016, p. 1705-1716.

研究成果: ジャーナルへの寄稿記事

Sugiyama, M, Oki, E, Nakaji, Y, Tsutsumi, S, Ono, N, Nakanishi, R, Sugiyama, M, Nakashima, Y, Sonoda, H, Ohgaki, K, Yamashita, N, Saeki, H, Okano, S, Kitao, H, Morita, M, Oda, Y & Maehara, Y 2016, 'High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer', Cancer Science, 巻. 107, 番号 11, pp. 1705-1716. https://doi.org/10.1111/cas.13075
Sugiyama, Masakazu ; Oki, Eiji ; Nakaji, Yu ; Tsutsumi, Satoshi ; Ono, Naomi ; Nakanishi, Ryota ; Sugiyama, Masahiko ; Nakashima, Yuichiro ; Sonoda, Hideto ; Ohgaki, Kippei ; Yamashita, Nami ; Saeki, Hiroshi ; Okano, Shinji ; Kitao, Hiroyuki ; Morita, Masaru ; Oda, Yoshinao ; Maehara, Yoshihiko. / High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer. :: Cancer Science. 2016 ; 巻 107, 番号 11. pp. 1705-1716.
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abstract = "The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse-free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32{\%}, 36{\%} and 32{\%} of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E-cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E-cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E-cadherin expression. In vitro studies suggested that RAS-MEK-MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.",
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T1 - High expression of the Notch ligand Jagged-1 is associated with poor prognosis after surgery for colorectal cancer

AU - Sugiyama, Masakazu

AU - Oki, Eiji

AU - Nakaji, Yu

AU - Tsutsumi, Satoshi

AU - Ono, Naomi

AU - Nakanishi, Ryota

AU - Sugiyama, Masahiko

AU - Nakashima, Yuichiro

AU - Sonoda, Hideto

AU - Ohgaki, Kippei

AU - Yamashita, Nami

AU - Saeki, Hiroshi

AU - Okano, Shinji

AU - Kitao, Hiroyuki

AU - Morita, Masaru

AU - Oda, Yoshinao

AU - Maehara, Yoshihiko

PY - 2016/11/1

Y1 - 2016/11/1

N2 - The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse-free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E-cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E-cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E-cadherin expression. In vitro studies suggested that RAS-MEK-MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.

AB - The importance of Notch signaling in colorectal cancer (CRC) carcinogenesis and progression has previously been presented. Increased expression of Jagged-1 (JAG1), a Notch ligand, in CRC has been revealed, but the detailed prognostic significance of JAG1 in CRC has not been determined. Protein expression of JAG1 was examined using immunohistochemistry in 158 CRC specimens. Expression of JAG1 and E-cadherin and their associations with clinicopathologic characteristics, overall survival (OS) and relapse-free survival (RFS) were evaluated. In vitro studies using compounds to regulate intracellular signaling and small interfering RNA to silence JAG1 were performed in a colon cancer cell line. JAG1 expression in cancerous tissues was weak, moderate or strong in 32%, 36% and 32% of specimens, respectively, and correlated with histologic type and T stage. In multivariate analysis, JAG1 expression, histologic type and lymphatic invasion independently correlated with OS and RFS. The combination of high JAG1 expression and low E-cadherin expression had an additive effect toward poorer OS and RFS compared with the low JAG1/high E-cadherin expression subtype. A significant correlation between JAG1 expression and KRAS status was detected in groups stratified as high E-cadherin expression. In vitro studies suggested that RAS-MEK-MAP kinase and the Wnt pathways positively regulated JAG1 expression. Gene silencing with siJAG1 indicated that JAG1 promotes the transition from epithelial to mesenchymal characteristics and cell growth. High expression of JAG1 is regulated by various pathways and is associated with poor prognosis through promoting the epithelial to mesenchymal transition and cell proliferation or maintaining cell survival in CRC.

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