Neogenin suppresses tumor progression and metastasis via inhibiting Merlin/YAP signaling

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Xiaohan Hu1, Li Li2, Fang Li3

  • 1Pediatric Clinical Research Institute, Children's Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China.

Cell Death Discovery
|February 6, 2023
PubMed

Insights

Neogenin (NEO1) acts as a tumor suppressor by inhibiting cancer growth and metastasis in colorectal cancer and glioma. It works by interacting with Merlin (NF2) to regulate the YAP pathway, suggesting its potential as a therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Tumor growth and metastasis are driven by the interplay between epithelial-mesenchymal transition (EMT) and cell cycle regulation.
  • Signaling receptors play a crucial role in mediating these cancer hallmarks.
  • Identifying key regulators is essential for understanding cancer progression and developing therapies.

Purpose of the Study:

  • To investigate the role of signaling receptors in EMT and cell cycle coordination across 33 cancer types.
  • To identify specific receptors that act as tumor suppressors by modulating these pathways.
  • To elucidate the mechanism by which Neogenin (NEO1) suppresses colorectal cancer (CRC) and Glioma.

Main Methods:

  • Nonlinear association analysis was performed on data from 33 cancer types.
  • The interaction between Neogenin (NEO1) and Merlin (NF2) was studied.
  • The effect of the Neogenin-Merlin complex on YAP phosphorylation was assessed.
  • Neogenin protein levels and their correlation with Merlin status and patient prognosis in CRC and Glioma were analyzed.

Main Results:

  • Most signaling receptors co-associated with EMT and cell cycle function as tumor suppressors.
  • Neogenin (NEO1) was identified as a key receptor inhibiting CRC and Glioma in situ growth and metastasis.
  • Neogenin forms a complex with Merlin (NF2), promoting YAP phosphorylation and suppressing oncogenic signaling.
  • Higher Neogenin levels correlate with better prognosis and Merlin status in CRC and Glioma.

Conclusions:

  • Neogenin acts as a tumor suppressor in CRC and Glioma by inhibiting the Merlin-YAP pathway.
  • Neogenin restricts oncogenic signaling, thereby limiting tumor growth and dissemination.
  • Neogenin represents a potential therapeutic candidate for CRC and Glioma treatment.

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