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Phosphorylation of TFCP2L1 by CDK1 is required for stem cell pluripotency and bladder carcinogenesis

Jinbeom Heo1,2, Byeong-Joo Noh3, Seungun Lee1,2

  • 1Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.

EMBO Molecular Medicine
|November 12, 2019
PubMed

Insights

Embryonic stem cell (ESC) factors like TFCP2L1 are reactivated in bladder cancer (BC). CDK1 phosphorylation of TFCP2L1 drives BC progression and poor survival, offering a potential therapeutic target.

Area of Science:

  • Molecular biology
  • Cancer research
  • Stem cell biology

Background:

  • Embryonic developmental programs are often reactivated in cancer, promoting dedifferentiation and metastasis.
  • The specific roles and regulation of these programs in oncogenesis are not fully understood.

Purpose of the Study:

  • To investigate the role of transcription factor TFCP2L1 and its regulation by CDK1 in embryonic stem cells (ESCs) and bladder cancer (BC).
  • To determine the clinical significance of the CDK1-TFCP2L1 pathway in BC progression.

Main Methods:

  • Analysis of protein interactome and transcription targets in murine ESCs.
  • Investigating the effect of CDK1 phosphorylation of TFCP2L1 on cell cycle, pluripotency, and differentiation.
  • Studying the CDK1-TFCP2L1 pathway in human BC cells and a xenograft model.
  • Correlating TFCP2L1 and CDK1 co-expression with clinical characteristics in BC patients.

Main Results:

  • CDK1 phosphorylates TFCP2L1 at Thr177, regulating ESC cell cycle, pluripotency, and differentiation.
  • The CDK1-TFCP2L1 pathway is aberrantly activated in BC, promoting proliferation, self-renewal, and invasion.
  • Loss of TFCP2L1 phosphorylation reduced BC cell tumorigenicity in vivo.
  • High TFCP2L1 and CDK1 co-expression in BC patients correlates with advanced tumor grade, invasion, metastasis, and predicts poor survival.

Conclusions:

  • CDK1-mediated phosphorylation of TFCP2L1 is a key regulator of stemness in both ESCs and BC.
  • This pathway drives aggressive features of bladder cancer and represents a potential prognostic and therapeutic target.
Keywords:
CDK1bladder cancerembryonic stem cellpluripotencystemness features

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