E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells

Yamin Qian, Xin Wu, Yuhki Yokoyama, Daisuke Okuzaki, Mai Taguchi, Haruka Hirose, Jiaqi Wang, Tsuyoshi Hata, Akira Inoue, Masayuki Hiraki, Masahisa Ohtsuka, Hidekazu Takahashi, Naotsugu Haraguchi, Tsunekazu Mizushima, Shinji Tanaka, Masaki Mori, Hirofumi Yamamoto

研究成果: ジャーナルへの寄稿記事

抄録

Cancer stem cells (CSC) are a subpopulation of tumor cells with properties of high tumorigenicity and drug resistance, which lead to recurrence and poor prognosis. Although a better understanding of CSC is essential for developing cancer therapies, scarcity of the CSC population has hindered such analyses. The aim of the present study was to elucidate whether the E-cadherin-Fc chimera protein (E-cad-Fc) enhances cancer stem-like properties because studies show that soluble E-cadherin stimulates human epithelial growth factor receptor (EGFR) and downstream signaling pathways that are reported to play a crucial role in CSC. For this purpose, we used ornithine decarboxylase (ODC)-degron–transduced (Degron(+)) KM12SM cells as a CSC model that retains relatively low CSC properties. Compared to cultures without E-cad-Fc treatment, we found that E-cad-Fc treatment further suppressed proteasome activity and largely enhanced cancer stem-like properties of ODC-degron–transduced KM12SM cells. These results include increased expression of stem cell markers Lgr5, Bmi-1, SOX9, CD44, and CD44v9, aldehyde dehydrogenase (ALDH), and enhancement of robust spheroid formation, and chemoresistance to 5-fluorouracil (5-FU) and oxaliplatin (L-OHP). These effects could be attributed to activation of the EGFR pathway as identified by extensive phosphorylation of EGFR, ERK, PI3K, AKT, and mTOR. In SW480 cells, E-cad-Fc matrix induced some CSC markers such as CD44v9 and ALDH. We also found that E-cad-Fc matrix showed high efficiency of inducing mesenchymal changes in colon cancer cells. Our data suggest that the E-cad-Fc matrix may enhance CSC properties such as enhancement of chemoresistance and sphere formation.

元の言語英語
ページ(範囲)3520-3532
ページ数13
ジャーナルCancer Science
110
発行部数11
DOI
出版物ステータス出版済み - 11 1 2019

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Neoplastic Stem Cells
Cadherins
Colonic Neoplasms
Growth Factor Receptors
Neoplasms
Proteins
oxaliplatin
Ornithine Decarboxylase
Proteasome Endopeptidase Complex
Phosphatidylinositol 3-Kinases
Drug Resistance
Fluorouracil
Stem Cells
Phosphorylation
Recurrence

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Qian, Y., Wu, X., Yokoyama, Y., Okuzaki, D., Taguchi, M., Hirose, H., ... Yamamoto, H. (2019). E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells. Cancer Science, 110(11), 3520-3532. https://doi.org/10.1111/cas.14193

E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells. / Qian, Yamin; Wu, Xin; Yokoyama, Yuhki; Okuzaki, Daisuke; Taguchi, Mai; Hirose, Haruka; Wang, Jiaqi; Hata, Tsuyoshi; Inoue, Akira; Hiraki, Masayuki; Ohtsuka, Masahisa; Takahashi, Hidekazu; Haraguchi, Naotsugu; Mizushima, Tsunekazu; Tanaka, Shinji; Mori, Masaki; Yamamoto, Hirofumi.

:: Cancer Science, 巻 110, 番号 11, 01.11.2019, p. 3520-3532.

研究成果: ジャーナルへの寄稿記事

Qian, Y, Wu, X, Yokoyama, Y, Okuzaki, D, Taguchi, M, Hirose, H, Wang, J, Hata, T, Inoue, A, Hiraki, M, Ohtsuka, M, Takahashi, H, Haraguchi, N, Mizushima, T, Tanaka, S, Mori, M & Yamamoto, H 2019, 'E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells', Cancer Science, 巻. 110, 番号 11, pp. 3520-3532. https://doi.org/10.1111/cas.14193
Qian, Yamin ; Wu, Xin ; Yokoyama, Yuhki ; Okuzaki, Daisuke ; Taguchi, Mai ; Hirose, Haruka ; Wang, Jiaqi ; Hata, Tsuyoshi ; Inoue, Akira ; Hiraki, Masayuki ; Ohtsuka, Masahisa ; Takahashi, Hidekazu ; Haraguchi, Naotsugu ; Mizushima, Tsunekazu ; Tanaka, Shinji ; Mori, Masaki ; Yamamoto, Hirofumi. / E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells. :: Cancer Science. 2019 ; 巻 110, 番号 11. pp. 3520-3532.
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T1 - E-cadherin-Fc chimera protein matrix enhances cancer stem-like properties and induces mesenchymal features in colon cancer cells

AU - Qian, Yamin

AU - Wu, Xin

AU - Yokoyama, Yuhki

AU - Okuzaki, Daisuke

AU - Taguchi, Mai

AU - Hirose, Haruka

AU - Wang, Jiaqi

AU - Hata, Tsuyoshi

AU - Inoue, Akira

AU - Hiraki, Masayuki

AU - Ohtsuka, Masahisa

AU - Takahashi, Hidekazu

AU - Haraguchi, Naotsugu

AU - Mizushima, Tsunekazu

AU - Tanaka, Shinji

AU - Mori, Masaki

AU - Yamamoto, Hirofumi

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