Related Experiment Video

Updated: Jan 1, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
11:32

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter

Published on: March 27, 2020

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Inhibition of TRPM7 blocks MRTF/SRF-dependent transcriptional and tumorigenic activity

Sandra Voringer1, Laura Schreyer1,2, Wiebke Nadolni1

  • 1Walther-Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians-Universität München, Munich, Germany.

Oncogene
|December 18, 2019
PubMed

Insights

Researchers found that blocking the TRPM7 channel inhibits hepatocellular carcinoma (HCC) growth by preventing MRTF-A from entering the nucleus. This TRPM7/MRTF pathway offers a new therapeutic strategy for HCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Myocardin-related transcription factors (MRTFs) and Serum Response Factor (SRF) regulate genes crucial for cell functions.
  • Aberrant MRTF/SRF activity is implicated in hepatocellular carcinoma (HCC) progression.
  • MRTF-A nuclear localization is essential for its oncogenic role in HCC.

Purpose of the Study:

  • To identify compounds inhibiting MRTF-A nuclear localization and transcriptional activity.
  • To investigate the role of TRPM7 in MRTF-mediated gene expression and HCC tumorigenesis.
  • To explore TRPM7 inhibition as a potential therapeutic strategy for HCC.

Main Methods:

  • Drug screening to identify inhibitors of MRTF-A nuclear localization.
  • Pharmacological inhibition and genome editing of TRPM7.
  • Analysis of RhoA activity, actin polymerization, and MRTF-A/SRF target gene expression.
  • In vitro and in vivo assessment of TRPM7 blockade effects on HCC cells and xenografts.

Main Results:

  • NS8593, a TRPM7 inhibitor, was identified as an MRTF-A nuclear export modulator.
  • TRPM7 regulates RhoA activity, actin polymerization, and MRTF-A/SRF transcriptional activity.
  • TRPM7 signaling involves Mg2+ influx and RhoA phosphorylation by its intrinsic kinase domain.
  • TRPM7 blockade induced oncogene-induced senescence in HCC cells and xenografts.

Conclusions:

  • TRPM7 plays a critical role in regulating MRTF-A activity and HCC growth.
  • TRPM7 inhibition effectively suppresses HCC progression both in vitro and in vivo.
  • The TRPM7/MRTF axis represents a novel and promising therapeutic target for hepatocellular carcinoma.

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