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Evaluation of role of Notch3 signaling pathway in human lung cancer cells

  • Original Article – Cancer Research
  • Published:
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Abstract

There is still a debate on the extent to which Notch3 signaling is involved in lung carcinogenesis and whether such function is dependent on cancer type or not.

Purpose

To evaluate Notch3 expression in different types of human lung cancer cells.

Methods

Notch3 was detected in human lung cancer cell lines and in tissues. Then, small interfering RNA (siRNA) was used to down-regulate the expression of Notch3 in H69AR small cell lung carcinoma (SCLC) cells; two non-small cell lung carcinoma (NSCLC) cells; A549 adenocarcinoma (ADC); and H2170 squamous cell carcinoma (SCC). In addition, Notch3 intracellular domain (N3ICD) plasmid was transfected into H1688 human SCLC cells. We observed the effect of deregulating Notch3 signaling on the following cell properties: Notch-related proteins, cell morphology, adhesion, epithelial-mesenchymal transition (EMT), motility, proliferation and neuroendocrine (NE) features of SCLC.

Results

Notch3 is mainly expressed in NSCLC, and the expression of Notch1, Hes1 and Jagged1 is affected by Notch3. Notch3 has opposite functions in SCLC and NSCLC, being a tumor suppressor in the former and tumor promoting in the latter, in the context of cell adhesion, EMT and motility. Regarding cell proliferation, we found that inhibiting Notch3 in NSCLC decreases cell proliferation and induces apoptosis in NSCLC. Notch3 has no effect on cell proliferation or NE features of SCLC.

Conclusion

Notch3 signaling in lung carcinoma is dependent on cell type. In SCLC, Notch3 behaves as a tumor suppressor pathway, while in NSCLC it acts as a tumor-promoting pathway.

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Acknowledgments

We thank Dr. Mitsuru Morimoto (Laboratory of Lung Development and Regeneration, RIKEN Center for Development Biology, Kobe, Japan), Dr. Koki Hasegawa and Prof. Kanako Niimori-Kita for their comments. We would like to thank Mrs. Motoko Kagayama, Mrs. Yuko Fukuchi-Nakaishi and Mrs. Takako Maeda for their technical assistance.

Funding

This study was partially funded by a Grant-in-Aid for Scientific Research (C; No. 25460439) from Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Authors and Affiliations

  1. Department of Pathology and Experimental Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan

    Wael Abdo Hassan, Shinji Kudoh, Yamato Motooka & Takaaki Ito

  2. Department of Pathology, Faculty of Medicine, Suez Canal University, Ismaïlia, Egypt

    Wael Abdo Hassan

  3. Department of Oral and Maxillofacial Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Ryoji Yoshida

  4. Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan

    Yamato Motooka

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  1. Wael Abdo Hassan
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  2. Ryoji Yoshida
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Correspondence to Takaaki Ito.

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The authors declare that they have no conflict of interest.

Ethical approval

Regarding the usage of human samples (formalin-fixed paraffin sections), the study followed the guidelines of the Ethics Committee of Kumamoto University (approval number 342).

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Hassan, W.A., Yoshida, R., Kudoh, S. et al. Evaluation of role of Notch3 signaling pathway in human lung cancer cells. J Cancer Res Clin Oncol 142, 981–993 (2016). https://doi.org/10.1007/s00432-016-2117-4

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  • DOI: https://doi.org/10.1007/s00432-016-2117-4

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