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RBPJ and MAML3: Potential Therapeutic Targets for Small Cell Lung Cancer

Hideya Onishi1, Shu Ichimiya2, Kosuke Yanai2

  • 1Department of Cancer Therapy and Research, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan ohnishi@surg1.med.kyushu-u.ac.jp.

Anticancer Research
|August 1, 2018
PubMed
Abstract

Insights

Targeting recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) inhibits small cell lung cancer (SCLC) cell proliferation and invasion. However, this approach may decrease sensitivity to chemotherapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Small cell lung cancer (SCLC) remains a significant challenge with limited effective treatments.
  • Recombination signal binding protein for immunoglobulin-kappa-J region (RBPJ) and mastermind-like 3 (MAML3) have emerged as potential therapeutic targets.
  • Previous research identified RBPJ and MAML3 as targets in pancreatic cancer.

Purpose of the Study:

  • To investigate the therapeutic potential of inhibiting RBPJ and MAML3 in SCLC.
  • To determine the effects of RBPJ/MAML3 inhibition on SCLC cell functions and chemosensitivity.

Main Methods:

  • Silencing of RBPJ and MAML3 in SBC-5 SCLC cells.
  • Assessment of cell proliferation, invasion, migration, and chemosensitivity.
  • Analysis of downstream signaling pathways, including Hedgehog and NOTCH.

Main Results:

  • RBPJ/MAML3 inhibition reduced Smoothened and HES1 expression, implicating Hedgehog and NOTCH pathways.
  • Inhibition significantly decreased SCLC cell proliferation and invasiveness by downregulating matrix metalloproteinases.
  • Chemosensitivity to cisplatin and gemcitabine was reduced following RBPJ/MAML3 inhibition.

Conclusions:

  • RBPJ and MAML3 represent promising novel therapeutic targets for SCLC.
  • Combined therapeutic strategies involving RBPJ/MAML3 inhibition may require careful consideration due to potential reductions in chemosensitivity.
Keywords:
MAML3RBPJSCLCtherapeutic target

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