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Notch1 controls cell invasion and metastasis in small cell lung carcinoma cell lines

Wael Abdo Hassan1, Ryoji Yoshida2, Shinji Kudoh3

  • 1Department of Pathology and Experimental Medicine, Kumamoto University, Graduate School of Medical Sciences, Japan; Department of Pathology, Faculty of Medicine, Suez Canal University, Egypt.

Lung Cancer (Amsterdam, Netherlands)
|December 3, 2014
PubMed
Abstract

Insights

Activating Notch1 signaling in small cell lung carcinoma (SCLC) inhibits cell invasion and metastasis. This finding suggests Notch1 activation as a potential therapeutic strategy for SCLC patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Signaling

Background:

  • Notch signaling is implicated in various human cancers, with context-dependent oncogenic or anti-proliferative roles.
  • The precise function of Notch signaling in small cell lung carcinoma (SCLC) remains incompletely understood.

Purpose of the Study:

  • To investigate the role of Notch1 signaling in human SCLC.
  • To determine the effect of Notch1 on SCLC cell invasion and metastasis.

Main Methods:

  • Down-regulation of Notch1 using small interfering RNA (siRNA) in SCLC cell lines (H69AR, SBC3).
  • Up-regulation of Notch1 via venus Notch1 intracellular domain (v.NICD) plasmid transfection in SCLC cell lines (H69, H1688).
  • In vivo studies using xenograft mouse models to assess tumor epithelial mesenchymal transition (EMT), cell motility, and metastatic potential.

Main Results:

  • Notch1 expression influences cell adhesion and EMT.
  • Overexpression of Notch1 in SCLC cells suppressed EMT, reduced cell motility, and decreased metastatic potential.

Conclusions:

  • Activation of the Notch1 signaling pathway demonstrates potential as a novel therapeutic strategy for SCLC.
  • Targeting Notch1 may offer a new avenue for treating human SCLC.
Keywords:
Cell metastatic potentialCell motilityEpithelial mesenchymal transition (EMT)Notch1 signalingSmall cell lung carcinoma (SCLC)Tail vein xenograft mouse model

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