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CDCA4/SERTAD1/E2F1 Facilitates Lung Adenocarcinoma Progression by Inhibiting PINK1/Parkin-Mediated Mitophagy

Jianlong Tan1, Jufen Wang2, Weidong Zhang1

  • 1Department of Respiratory Medicine, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, China.

IUBMB Life
|October 25, 2025
PubMed

Insights

Cell division cycle-associated protein 4 (CDCA4) inhibits mitophagy in lung adenocarcinoma (LUAD). Silencing CDCA4 promotes mitophagy, suppresses tumor growth, and offers a potential therapeutic target for LUAD.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background:

  • Cell division cycle-associated protein 4 (CDCA4) is implicated in lung adenocarcinoma (LUAD) development.
  • The specific role of CDCA4 in regulating mitophagy, a key cellular degradation process, is not well understood.

Purpose of the Study:

  • To investigate the regulatory role of CDCA4 in mitophagy within LUAD.
  • To explore the therapeutic potential of targeting CDCA4 in LUAD treatment.

Main Methods:

  • CDCA4 expression levels were analyzed in LUAD tissues and correlated with mitophagy activity.
  • Lentiviral vectors were used to silence CDCA4 in LUAD cells, followed by treatments with chloroquine and rapamycin.
  • Mitochondrial function, apoptosis, proliferation, and migration were assessed.
  • Protein-protein interactions involving CDCA4, SERTAD1, and E2F1 were investigated.
  • In vivo studies involved injecting CDCA4-silenced LUAD cells into immunodeficient mice.

Main Results:

  • CDCA4 expression was elevated in LUAD and inversely correlated with mitophagy.
  • CDCA4 knockdown promoted mitophagy by activating the PINK1/Parkin pathway and enhancing mitochondrial degradation.
  • Silencing CDCA4 suppressed LUAD cell proliferation and migration, effects modulated by lysosomal inhibition and autophagy induction.
  • CDCA4 was found to interact with and stabilize SERTAD1 and E2F1, hindering mitophagy promotion.
  • In vivo, CDCA4-silenced xenografts showed reduced tumor growth, increased apoptosis, and enhanced mitophagy.

Conclusions:

  • CDCA4 acts as a mitophagy inhibitor in LUAD, potentially through the CDCA4/SERTAD1/E2F1 complex.
  • Targeting this CDCA4-mediated pathway presents a novel therapeutic strategy for LUAD.
Keywords:
CDCA4PINK1/Parkinautophagylung adenocarcinomamitochondria

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