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NDRG1 regulates Filopodia-induced Colorectal Cancer invasiveness via modulating CDC42 activity

Batuer Aikemu1,2,3, Yanfei Shao1,2,3, Guang Yang1,2,3

  • 1Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

International Journal of Biological Sciences
|May 17, 2021
PubMed

Insights

N-myc downstream regulated gene-1 (NDRG1) suppresses colorectal cancer (CRC) invasion by regulating cell division cycle-42 (CDC42) activity and actin reorganization. NDRG1 loss promotes CRC cell dissemination and correlates with advanced cancer stages.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • N-myc downstream regulated gene-1 (NDRG1) is a known metastasis suppressor.
  • The precise mechanisms by which NDRG1 influences tumor invasion remain unclear.

Purpose of the Study:

  • To investigate the role of NDRG1 in colorectal cancer (CRC) invasion and its underlying molecular mechanisms.
  • To elucidate the relationship between NDRG1, cell division cycle-42 (CDC42), and cytoskeleton dynamics in CRC.

Main Methods:

  • In silico analysis to predict NDRG1's role in actin reorganization.
  • In vitro experiments using NDRG1-modified CRC cell lines.
  • In vivo studies assessing CRC cell dissemination.
  • Clinical sample analysis to correlate NDRG1 and CDC42 expression with cancer stage.

Main Results:

  • NDRG1 knockdown altered filopodia formation and led to excessive CDC42 activation in CRC cells.
  • NDRG1 loss disrupted RhoGDIα-CDC42 binding, activating the PAK1/Cofilin pathway and promoting invasion.
  • NDRG1 silencing enhanced CRC cell dissemination in vivo.
  • Active CDC42 levels were elevated in advanced T stage CRC patients and inversely correlated with NDRG1 expression.

Conclusions:

  • NDRG1 regulates CRC invasion by controlling CDC42 activity and cytoskeleton reorganization.
  • This study uncovers a novel mechanism involving NDRG1, CDC42, and actin dynamics in cancer metastasis.
  • Findings suggest NDRG1 as a potential therapeutic target for inhibiting CRC invasion and dissemination.
Keywords:
CDC42NDRG1colorectal cancercytoskeletoninvasion

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