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Identifying TP53RK as a key regulator of colorectal cancer survival and a potential therapeutic target

Younghee Choi1,2, Seowoo Park1,2, Seojin Yang1

  • 1Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 03080, Republic of Korea.

Scientific Reports
|October 16, 2025
PubMed

Insights

TP53-regulating kinase (TP53RK) is a novel therapeutic target for colorectal cancer (CRC). This kinase regulates DNA replication and genomic stability, making it crucial for CRC cell survival and proliferation.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Colorectal cancer (CRC) remains a significant cause of cancer mortality globally.
  • Novel therapeutic strategies are urgently needed to combat CRC.
  • Understanding the molecular mechanisms driving CRC progression is essential for developing effective treatments.

Purpose of the Study:

  • To identify novel regulators of colorectal cancer (CRC) cell survival and proliferation.
  • To investigate the role of TP53-regulating kinase (TP53RK) in CRC pathogenesis.
  • To explore the therapeutic potential of targeting the TP53RK pathway in CRC.

Main Methods:

  • Utilized a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 library screen targeting serine/threonine kinase-related genes.
  • Performed functional validation studies including gene depletion and analysis of DNA replication stress, apoptosis, and cell cycle.
  • Investigated the mechanistic link between TP53RK, cell division cycle 7 (CDC7), and minichromosome maintenance complex protein (MCM) phosphorylation.

Main Results:

  • TP53RK was identified as a critical regulator of CRC cell survival and proliferation, significantly overexpressed in CRC tissues.
  • TP53RK depletion induced DNA replication stress, apoptosis, and cell cycle arrest, independent of p53 status.
  • TP53RK stabilizes CDC7, promoting MCM phosphorylation and replication fork progression; its disruption impairs DNA replication dynamics and sensitizes cells to replication stress and CDC7 inhibition.

Conclusions:

  • TP53RK is a pivotal regulator of DNA replication fidelity and genomic stability in colorectal cancer.
  • The TP53RK-CDC7 axis represents a promising therapeutic target for CRC treatment.
  • Targeting TP53RK may offer a novel strategy to enhance the efficacy of existing therapies or overcome resistance in CRC.
Keywords:
CDC7TP53RKCRISPR/Cas9 screeningColorectal cancerDNA replication

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