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Updated: Mar 12, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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Phospholipase D1 Acts through Akt/TopBP1 and RB1 to Regulate the E2F1-Dependent Apoptotic Program in Cancer Cells

Dong Woo Kang1,2, Shin Wha Lee1,3, Won Chan Hwang2

  • 1Institute of Innovative Cancer Research, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Cancer Research
|October 30, 2016
PubMed

Insights

Phospholipase D1 (PLD1) links key cancer pathways in colorectal cancer. Targeting PLD1 promotes apoptosis and may offer a new therapeutic strategy for colon cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Signaling

Background:

  • The RB1/E2F1 pathway is frequently altered in colorectal cancer (CRC).
  • Potential links between RB1/E2F1, Wnt/β-catenin, and PI3K/Akt pathways in CRC are suggested but lack molecular evidence.

Purpose of the Study:

  • To investigate the role of phospholipase D1 (PLD1) in mediating interactions between major signaling pathways in colorectal cancer development.
  • To explore PLD1 as a potential therapeutic target in colon cancer.

Main Methods:

  • Utilized the Apcmin/+ mouse model for intestinal tumorigenesis studies.
  • Investigated PLD1's role in apoptosis, cell survival, and cancer-initiating cell self-renewal.
  • Analyzed the miR-192/4465-RB1 axis and Akt-TopBP1 pathways.
  • Correlated PLD1-driven E2F1 target gene expression with tumor stage in CRC patients.

Main Results:

  • PLD1, a β-catenin/TCF4 target, orchestrates functional interactions between Wnt/β-catenin, PI3K/Akt, and RB1/E2F1 pathways.
  • PLD1 overexpression protected intestinal cells from apoptosis in the Apcmin/+ model.
  • Targeting PLD1 induced E2F1-dependent apoptosis via miR-192/4465-mediated RB1 downregulation and Akt-TopBP1 inhibition.
  • PLD1 also contributed to colon cancer-initiating cell self-renewal through the miRNA-RB1 axis and Akt pathway.
  • PLD1-driven E2F1 target gene expression correlated with advanced colorectal cancer stage.

Conclusions:

  • PLD1 acts as a crucial signaling node, mediating cross-talk between major pathways to enhance colon cancer cell survival and malignancy.
  • PLD1 represents a promising therapeutic target for colorectal cancer treatment.

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