Hedgehog inhibition upregulates TRK expression to antagonize tumor suppression in small cell lung cancer cells

Hideya Ohnishi, Katsuya Nakamura, Shuntaro Nagai, Kosuke Yanai, Akio Yamasaki, Makoto Kawamoto, Akira Imaizumi, Takashi Morisaki

研究成果: ジャーナルへの寄稿記事

3 引用 (Scopus)

抄録

Background/Aim: Previously we have shown that tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signalling pathways induce malignant phenotypes in many cancer types. However, results from small cell lung cancer (SCLC) clinical trials using TRK and Hh inhibitors have been disappointing. One reason for this may be the existence of crosstalk between TRKB and Hh signalling pathways. In this study, we detected negative crosstalk between the TRKB and Hh-GLI1 signalling pathways. Materials and Methods: The human small cell lung carcinoma cell line, SBC-5, was used. Using small interfering RNA to inhibit TRKB and Hh signalling, whether TRKB and Hh signaling contribute to proliferation and invasiveness in SBC-5 cells were investigated. Results: TRKB expression in GLI1 siRNAtransfected SBC-5 cells was higher than that of control cells. GLI1-knockdown alone did not affect invasiveness of SBC-5 cells. However, combined knockdown of TRKB and GLI1 significantly decreased invasiveness. Moreover, combined TRKB and GLI1 knockdown inhibited proliferation and migration to a greater extent than when either was inhibited alone. Conclusion: These results suggest that Hh inhibition increases TrkB expression to counter tumor suppression in SBC-5 cells. The combined use of TRKB and Hh inhibitors may, therefore, be useful for the treatment of refractory SCLC.

元の言語英語
ページ(範囲)4987-4992
ページ数6
ジャーナルAnticancer Research
37
発行部数9
DOI
出版物ステータス出版済み - 9 1 2017

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Small Cell Lung Carcinoma
Up-Regulation
Neoplasms
tropomyosin kinase
Small Interfering RNA
Clinical Trials
Phenotype
Cell Line

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

これを引用

Hedgehog inhibition upregulates TRK expression to antagonize tumor suppression in small cell lung cancer cells. / Ohnishi, Hideya; Nakamura, Katsuya; Nagai, Shuntaro; Yanai, Kosuke; Yamasaki, Akio; Kawamoto, Makoto; Imaizumi, Akira; Morisaki, Takashi.

:: Anticancer Research, 巻 37, 番号 9, 01.09.2017, p. 4987-4992.

研究成果: ジャーナルへの寄稿記事

Ohnishi, Hideya ; Nakamura, Katsuya ; Nagai, Shuntaro ; Yanai, Kosuke ; Yamasaki, Akio ; Kawamoto, Makoto ; Imaizumi, Akira ; Morisaki, Takashi. / Hedgehog inhibition upregulates TRK expression to antagonize tumor suppression in small cell lung cancer cells. :: Anticancer Research. 2017 ; 巻 37, 番号 9. pp. 4987-4992.
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abstract = "Background/Aim: Previously we have shown that tropomyosin-related kinase B (TRKB) and Hedgehog (Hh) signalling pathways induce malignant phenotypes in many cancer types. However, results from small cell lung cancer (SCLC) clinical trials using TRK and Hh inhibitors have been disappointing. One reason for this may be the existence of crosstalk between TRKB and Hh signalling pathways. In this study, we detected negative crosstalk between the TRKB and Hh-GLI1 signalling pathways. Materials and Methods: The human small cell lung carcinoma cell line, SBC-5, was used. Using small interfering RNA to inhibit TRKB and Hh signalling, whether TRKB and Hh signaling contribute to proliferation and invasiveness in SBC-5 cells were investigated. Results: TRKB expression in GLI1 siRNAtransfected SBC-5 cells was higher than that of control cells. GLI1-knockdown alone did not affect invasiveness of SBC-5 cells. However, combined knockdown of TRKB and GLI1 significantly decreased invasiveness. Moreover, combined TRKB and GLI1 knockdown inhibited proliferation and migration to a greater extent than when either was inhibited alone. Conclusion: These results suggest that Hh inhibition increases TrkB expression to counter tumor suppression in SBC-5 cells. The combined use of TRKB and Hh inhibitors may, therefore, be useful for the treatment of refractory SCLC.",
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AU - Ohnishi, Hideya

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AU - Yamasaki, Akio

AU - Kawamoto, Makoto

AU - Imaizumi, Akira

AU - Morisaki, Takashi

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