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ROR2 promotes cell cycle progression and cell proliferation through the PI3K/AKT signaling pathway in gastric cancer

Qi Liu1, Xin Zhao2, Xiaowen Shao2

  • 1Medical Research and Laboratory Diagnostic Center, Jinan Central Hospital, Shandong University, Jinan, China.

Molecular Carcinogenesis
|August 16, 2024
PubMed

Insights

Receptor tyrosine kinase-like orphan receptor 2 (ROR2) promotes gastric cancer (GC) cell proliferation by activating the PI3K/AKT/mTOR/S6K pathway and accelerating the G2/M phase cell cycle. ROR2 expression correlates with Twist1 and poorer survival in GC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Gastric cancer (GC) progression is characterized by uncontrolled cell proliferation.
  • Abnormal expression of receptor tyrosine kinase-like orphan receptor 2 (ROR2) is implicated in tumor growth.
  • Previous bioinformatics analysis suggested a link between ROR2 and the G2/M phase of the GC cell cycle.

Purpose of the Study:

  • To investigate the regulatory role of ROR2 in gastric cancer (GC) cell proliferation.
  • To elucidate the molecular mechanisms underlying ROR2's effect on the GC cell cycle.

Main Methods:

  • Bioinformatics analysis to identify associations between ROR2 and cell cycle phases.
  • Experimental validation in GC cell lines and mouse xenograft models.
  • Analysis of ROR2 and Twist1 expression in human GC tissues.

Main Results:

  • ROR2, transcribed by Twist1, activates the PI3K/AKT/mTOR/S6K signaling pathway.
  • This activation accelerates the G2/M phase transition, promoting GC cell proliferation.
  • A functional link between ROR2, Twist1, and the G2/M phase was confirmed in vivo and in human tissues.
  • ROR2 expression positively correlated with Twist1 expression and negatively with patient survival.

Conclusions:

  • ROR2 plays a significant role in promoting gastric cancer cell proliferation via the PI3K/AKT/mTOR/S6K pathway and cell cycle regulation.
  • The ROR2-Twist1 axis is crucial for GC progression and is associated with poor prognosis.
  • ROR2 represents a potential therapeutic target for gastric cancer management.
Keywords:
GCROR2Twist1cell cycleproliferation

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