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Updated: May 27, 2025

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The splicing factor SRRM2 modulates two S6K kinases to promote colorectal cancer growth

Zhengwei Yan1, Luling He1, Jiawei Yuan1

  • 1Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, China.

Oncogene
|February 16, 2025
PubMed

Insights

The splicing factor SRRM2 activates the mTOR-S6K pathway by regulating S6K1 and S6K2 protein levels. SRRM2 promotes colorectal cancer growth and may be a therapeutic target.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cellular Metabolism

Background:

  • The mechanistic target of rapamycin (mTOR) pathway is crucial for cell growth and metabolism.
  • Ribosomal protein S6 kinases (S6K1 and S6K2) are key effectors of the mTOR pathway, regulating translation efficiency.
  • The precise regulatory mechanisms governing mTOR-S6K signaling remain incompletely understood.

Purpose of the Study:

  • To identify novel regulators of the mTOR pathway.
  • To investigate the role of the splicing factor SRRM2 in modulating S6K1 and S6K2 levels.
  • To explore the potential oncogenic function of SRRM2 in colorectal cancer (CRC).

Main Methods:

  • Bioinformatic analysis to identify potential mTOR regulators.
  • Experimental validation of SRRM2's effects on S6K1 and S6K2 expression and stability.
  • Assessment of SRRM2 expression in CRC tissues and its correlation with patient prognosis.
  • In vitro and in vivo studies to evaluate SRRM2's role in CRC cell proliferation.

Main Results:

  • SRRM2 was identified as a modulator of S6K1 and S6K2 protein levels, activating the mTOR-S6K pathway.
  • SRRM2 enhances S6K2 expression via alternative splicing and increases S6K1 stability by regulating WWP2.
  • High SRRM2 expression in CRC tissues correlates with poor prognosis.
  • SRRM2 promotes CRC growth both in vitro and in vivo.

Conclusions:

  • SRRM2 oncogenically drives colorectal cancer progression by activating the mTOR-S6K pathway through distinct mechanisms.
  • SRRM2's dual regulation of S6K1 and S6K2 highlights its significant role in CRC.
  • SRRM2 emerges as a promising therapeutic target for colorectal cancer treatment.

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