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CK1δ/ε inhibition induces ULK1-mediated autophagy in tumorigenesis

Vivian Weiwen Xue1, Shanshan Liu2, Qi Sun2

  • 1Department of Pharmacology, Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Marshall Laboratory of Biomedical Engineering, Shenzhen University Health Science Center, No. 1066 Xueyuan Avenue, Nanshan District, Shenzhen 518060, China; College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen, China.

Translational Oncology
|January 7, 2024
PubMed
Abstract

Insights

Casein kinase I delta/epsilon (CK1δ/ε) regulates autophagy via ULK1, suppressing cancer cell proliferation. Inhibiting CK1δ/ε halts tumor growth, highlighting its therapeutic potential.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Autophagy Research

Background:

  • Autophagy is crucial for maintaining cellular homeostasis.
  • Casein kinase I (CK1) family members are implicated in tumorigenesis.
  • The precise role of CK1δ/ε in autophagy regulation is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which CK1δ/ε regulates autophagy.
  • To investigate the impact of CK1δ/ε on cancer cell growth and proliferation.
  • To assess the therapeutic potential of CK1δ/ε inhibition in cancer.

Main Methods:

  • Silencing of CK1δ/ε in cancer cell lines.
  • Analysis of autophagy-related gene expression and autophagic flux.
  • In vivo studies using a syngeneic mouse model of lung cancer.

Main Results:

  • CK1δ/ε silencing enhances ULK1-mediated autophagy and suppresses cancer cell proliferation.
  • ULK1 knockdown counteracts the autophagic activation induced by CK1δ/ε inhibition.
  • Inhibition of CK1δ/ε significantly suppresses tumor growth in vivo.

Conclusions:

  • CK1δ/ε plays a key role in regulating tumorigenesis through ULK1-mediated autophagy.
  • CK1δ/ε inhibition demonstrates significant anti-tumor effects.
  • CK1δ/ε represents a promising therapeutic target for cancer treatment.
Keywords:
AutophagyCK1δ/εTumorigenesisULK1

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