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eEF2K-Mediated Stabilization of PCBP2 Promotes Oncogenic mRNA Programs in Triple-Negative Breast Cancer

Yueying Cheng1,2, Ting Jiang1,2, Wenqian Zhu3

  • 1Department of Pharmacy, The Second Xiangya Hospital, Central South University, Changsha, 410011, China.

International Journal of Biological Sciences
|April 20, 2026
PubMed

Insights

Triple-negative breast cancer (TNBC) progression is driven by the eEF2K-PCBP2 signaling axis. Targeting this pathway offers a new therapeutic strategy for TNBC, a challenging disease with limited treatment options.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Triple-negative breast cancer (TNBC) lacks targeted therapies and has a poor prognosis.
  • Eukaryotic elongation factor 2 kinase (eEF2K) is upregulated in TNBC and promotes tumor growth.
  • The exact mechanisms of eEF2K's oncogenic role in TNBC are not fully understood.

Purpose of the Study:

  • Identify novel downstream targets of eEF2K in TNBC.
  • Elucidate the role of eEF2K-mediated signaling in TNBC progression.
  • Evaluate the eEF2K-PCBP2 axis as a potential therapeutic target for TNBC.

Main Methods:

  • Identified poly(rC)-binding protein 2 (PCBP2) as a downstream substrate of eEF2K.
  • Analyzed clinical TNBC specimens for eEF2K and PCBP2 expression.
  • Investigated the effect of PCBP2 phosphorylation at Ser189 on TNBC cell malignancy.
  • Examined the mechanism of PCBP2 stabilization by eEF2K-mediated phosphorylation.
  • Assessed the impact of PCBP2 on the mRNA stability of oncogenic genes (TNC, SOX5, ITGB3).

Main Results:

  • PCBP2 was identified as a novel downstream substrate of eEF2K in TNBC.
  • Positive correlation observed between eEF2K and PCBP2 protein levels in clinical TNBC samples.
  • Phosphorylation of PCBP2 at Ser189 by eEF2K stabilized PCBP2, preventing its degradation.
  • Stabilized PCBP2 enhanced the mRNA stability of pro-oncogenic genes TNC, SOX5, and ITGB3, promoting TNBC progression.

Conclusions:

  • PCBP2 is a critical downstream effector of eEF2K in TNBC.
  • The eEF2K-PCBP2 signaling pathway plays a key role in driving TNBC progression.
  • The eEF2K-PCBP2 axis represents a promising therapeutic target for TNBC treatment.
Keywords:
PCBP2eEF2KmRNA stabilitytriple-negative breast cancerubiquitin-proteasome degradation

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