Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor,

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Updated: Nov 28, 2025

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
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Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

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Teppei Sugano1,2, Mari Masuda1, Fumitaka Takeshita3

  • 1Division of Chemotherapy and Clinical Research, National Cancer Center Research Institute, Tokyo, 104-0045, Japan.

British Journal of Cancer
|November 27, 2020
PubMed
Abstract

Insights

A novel TNIK inhibitor, NCB-0846, effectively blocks cancer cell metastasis by inhibiting TGFβ-induced EMT. This drug targets TGFβ signaling, offering a promising strategy for preventing lung cancer spread.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Metastasis is a leading cause of cancer mortality, with epithelial to mesenchymal transition (EMT) playing a key role.
  • Targeting EMT presents a promising therapeutic strategy for managing cancer metastasis.

Purpose of the Study:

  • To investigate the effects of a small-molecule TNIK inhibitor (NCB-0846) on TGFβ1-induced EMT in lung cancer cells.
  • To explore the potential of targeting TNIK for the prevention of cancer metastasis.

Main Methods:

  • Utilized A549 lung cancer cells and examined the impact of NCB-0846 on TGFβ1-induced EMT.
  • Assessed SMAD2/3 phosphorylation and nuclear translocation.
  • Evaluated the in vivo efficacy of NCB-0846 in a mouse model of lung metastasis.
  • Investigated the role of microRNAs in mediating the suppression of TGFβ receptor type-I (TGFBR1) expression.

Main Results:

  • NCB-0846 significantly inhibited TGFβ1-induced EMT in A549 cells.
  • Inhibition of EMT correlated with reduced SMAD2/3 phosphorylation and nuclear translocation.
  • NCB-0846 abolished lung metastasis in vivo.
  • The drug's action involved downregulation of TGFBR1 expression, partly via miR-320 and miR-186 induction.

Conclusions:

  • NCB-0846 effectively inhibits TGFβ/SMAD signaling and EMT in lung cancer cells.
  • The mechanism involves transcriptional downregulation of TGFBR1.
  • NCB-0846 shows potential as a therapeutic agent for preventing lung cancer metastasis.

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