Critical roles of Wnt5a–Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloproteinase-2 via ΔNp63β-mediated epithelial–mesenchymal transition

Taiki Sakamoto, Shintarou Kawano, Ryota Matsubara, Yuichi Goto, Teppei Jinno, Yasuyuki Maruse, Naoki Kaneko, Yuma Hashiguchi, Taichi Hattori, Shoichi Tanaka, ryoji kitamura, Tamotsu Kiyoshima, Seiji Nakamura

研究成果: ジャーナルへの寄稿記事

5 引用 (Scopus)

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Objectives We previously showed that ΔNp63β, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63β affects cell motility. As the results, Wnt5a was significantly down-regulated by ΔNp63β overexpression in tongue SCC cell line (SQUU-B) with EMT phenotype. Materials and methods Seven OSCC cell lines were used. Expression of ΔNp63, Wnt5a, its receptor Ror2, and matrix metalloproteinases (MMPs) were analyzed by RT-PCR, real-time PCR, and western blotting, and gelatin zymography. Furthermore, we examined the effects of siRNA for Wnt5a or Ror2 and recombinant human Wnt5a (rhWnt5a) on motility of tongue SCC cells. Biopsy specimens from tongue SCC patients were used for immunohistochemical staining of Wnt5a and Ror2. Results Wnt5a and Ror2 were expressed only in SQUU-B cells without ΔNp63 expression, and negatively associated with ΔNp63 expression in other cells. ΔNp63β overexpression in SQUU-B cells decreased Wnt5a and Ror2 expression. By Wnt5a or Ror2 knockdown, cell motility was remarkably inhibited, but EMT markers expression was unaffected. MMP-2 expression and the activities inversely correlated with ΔNp63 expression, and were inhibited by Wnt5a or Ror2 knockdown. Cell motility and MMP-2 activities were recovered by adding rhWnt5a in the cells with Wnt5a knockdown, but not in those with Ror2 knockdown. Moreover, immunohistochemical analyses in tongue SCC specimens found that high expression of Wnt5a or Ror2 was associated with poorer prognosis. Conclusion Wnt5a–Ror2 signaling enhanced tongue SCC cell aggressiveness and promoted production of MMP-2 following ΔNp63β-mediated EMT.

元の言語英語
ページ(範囲)15-25
ページ数11
ジャーナルOral Oncology
69
DOI
出版物ステータス出版済み - 6 1 2017

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Matrix Metalloproteinase 2
Tongue
Squamous Cell Carcinoma
Cell Movement
B-Lymphocytes
Cell Line
Gelatin
Oligonucleotide Array Sequence Analysis
Matrix Metalloproteinases
Small Interfering RNA
Real-Time Polymerase Chain Reaction
Western Blotting
Staining and Labeling
Phenotype
Biopsy
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oral Surgery
  • Oncology
  • Cancer Research

これを引用

@article{55bf6fa0269845b1919951fc37f92b17,
title = "Critical roles of Wnt5a–Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloproteinase-2 via ΔNp63β-mediated epithelial–mesenchymal transition",
abstract = "Objectives We previously showed that ΔNp63β, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63β affects cell motility. As the results, Wnt5a was significantly down-regulated by ΔNp63β overexpression in tongue SCC cell line (SQUU-B) with EMT phenotype. Materials and methods Seven OSCC cell lines were used. Expression of ΔNp63, Wnt5a, its receptor Ror2, and matrix metalloproteinases (MMPs) were analyzed by RT-PCR, real-time PCR, and western blotting, and gelatin zymography. Furthermore, we examined the effects of siRNA for Wnt5a or Ror2 and recombinant human Wnt5a (rhWnt5a) on motility of tongue SCC cells. Biopsy specimens from tongue SCC patients were used for immunohistochemical staining of Wnt5a and Ror2. Results Wnt5a and Ror2 were expressed only in SQUU-B cells without ΔNp63 expression, and negatively associated with ΔNp63 expression in other cells. ΔNp63β overexpression in SQUU-B cells decreased Wnt5a and Ror2 expression. By Wnt5a or Ror2 knockdown, cell motility was remarkably inhibited, but EMT markers expression was unaffected. MMP-2 expression and the activities inversely correlated with ΔNp63 expression, and were inhibited by Wnt5a or Ror2 knockdown. Cell motility and MMP-2 activities were recovered by adding rhWnt5a in the cells with Wnt5a knockdown, but not in those with Ror2 knockdown. Moreover, immunohistochemical analyses in tongue SCC specimens found that high expression of Wnt5a or Ror2 was associated with poorer prognosis. Conclusion Wnt5a–Ror2 signaling enhanced tongue SCC cell aggressiveness and promoted production of MMP-2 following ΔNp63β-mediated EMT.",
author = "Taiki Sakamoto and Shintarou Kawano and Ryota Matsubara and Yuichi Goto and Teppei Jinno and Yasuyuki Maruse and Naoki Kaneko and Yuma Hashiguchi and Taichi Hattori and Shoichi Tanaka and ryoji kitamura and Tamotsu Kiyoshima and Seiji Nakamura",
year = "2017",
month = "6",
day = "1",
doi = "10.1016/j.oraloncology.2017.03.019",
language = "English",
volume = "69",
pages = "15--25",
journal = "Oral Oncology",
issn = "1368-8375",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Critical roles of Wnt5a–Ror2 signaling in aggressiveness of tongue squamous cell carcinoma and production of matrix metalloproteinase-2 via ΔNp63β-mediated epithelial–mesenchymal transition

AU - Sakamoto, Taiki

AU - Kawano, Shintarou

AU - Matsubara, Ryota

AU - Goto, Yuichi

AU - Jinno, Teppei

AU - Maruse, Yasuyuki

AU - Kaneko, Naoki

AU - Hashiguchi, Yuma

AU - Hattori, Taichi

AU - Tanaka, Shoichi

AU - kitamura, ryoji

AU - Kiyoshima, Tamotsu

AU - Nakamura, Seiji

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Objectives We previously showed that ΔNp63β, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63β affects cell motility. As the results, Wnt5a was significantly down-regulated by ΔNp63β overexpression in tongue SCC cell line (SQUU-B) with EMT phenotype. Materials and methods Seven OSCC cell lines were used. Expression of ΔNp63, Wnt5a, its receptor Ror2, and matrix metalloproteinases (MMPs) were analyzed by RT-PCR, real-time PCR, and western blotting, and gelatin zymography. Furthermore, we examined the effects of siRNA for Wnt5a or Ror2 and recombinant human Wnt5a (rhWnt5a) on motility of tongue SCC cells. Biopsy specimens from tongue SCC patients were used for immunohistochemical staining of Wnt5a and Ror2. Results Wnt5a and Ror2 were expressed only in SQUU-B cells without ΔNp63 expression, and negatively associated with ΔNp63 expression in other cells. ΔNp63β overexpression in SQUU-B cells decreased Wnt5a and Ror2 expression. By Wnt5a or Ror2 knockdown, cell motility was remarkably inhibited, but EMT markers expression was unaffected. MMP-2 expression and the activities inversely correlated with ΔNp63 expression, and were inhibited by Wnt5a or Ror2 knockdown. Cell motility and MMP-2 activities were recovered by adding rhWnt5a in the cells with Wnt5a knockdown, but not in those with Ror2 knockdown. Moreover, immunohistochemical analyses in tongue SCC specimens found that high expression of Wnt5a or Ror2 was associated with poorer prognosis. Conclusion Wnt5a–Ror2 signaling enhanced tongue SCC cell aggressiveness and promoted production of MMP-2 following ΔNp63β-mediated EMT.

AB - Objectives We previously showed that ΔNp63β, a splicing variant of ΔNp63, mediated EMT and affected cell motility. DNA microarray was thus performed to elucidate the mechanism that ΔNp63β affects cell motility. As the results, Wnt5a was significantly down-regulated by ΔNp63β overexpression in tongue SCC cell line (SQUU-B) with EMT phenotype. Materials and methods Seven OSCC cell lines were used. Expression of ΔNp63, Wnt5a, its receptor Ror2, and matrix metalloproteinases (MMPs) were analyzed by RT-PCR, real-time PCR, and western blotting, and gelatin zymography. Furthermore, we examined the effects of siRNA for Wnt5a or Ror2 and recombinant human Wnt5a (rhWnt5a) on motility of tongue SCC cells. Biopsy specimens from tongue SCC patients were used for immunohistochemical staining of Wnt5a and Ror2. Results Wnt5a and Ror2 were expressed only in SQUU-B cells without ΔNp63 expression, and negatively associated with ΔNp63 expression in other cells. ΔNp63β overexpression in SQUU-B cells decreased Wnt5a and Ror2 expression. By Wnt5a or Ror2 knockdown, cell motility was remarkably inhibited, but EMT markers expression was unaffected. MMP-2 expression and the activities inversely correlated with ΔNp63 expression, and were inhibited by Wnt5a or Ror2 knockdown. Cell motility and MMP-2 activities were recovered by adding rhWnt5a in the cells with Wnt5a knockdown, but not in those with Ror2 knockdown. Moreover, immunohistochemical analyses in tongue SCC specimens found that high expression of Wnt5a or Ror2 was associated with poorer prognosis. Conclusion Wnt5a–Ror2 signaling enhanced tongue SCC cell aggressiveness and promoted production of MMP-2 following ΔNp63β-mediated EMT.

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U2 - 10.1016/j.oraloncology.2017.03.019

DO - 10.1016/j.oraloncology.2017.03.019

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C2 - 28559016

AN - SCOPUS:85016926695

VL - 69

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JO - Oral Oncology

JF - Oral Oncology

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