What question did this study set out to answer?

This research investigates the role of phospholipase D1 (PLD1) in driving metabolic resistance and survival in cervical squamous cell carcinoma (SCC).

April 5, 2026

Abstract 1275: Phospholipase D1 overexpression drives metabolic survival and stress resistance in cervical cancer.

Key Points

This research investigates the role of phospholipase D1 (PLD1) in driving metabolic resistance and survival in cervical squamous cell carcinoma (SCC).
Evaluated PLD1 expression using TCGA datasets and validated with primary cervical tumors through qRT-PCR, PLD activity assays, and immunohistochemistry.
Conducted functional studies with PLD1 knockdown via shRNA and a selective inhibitor in primary SCC and adenocarcinoma cells.
Measured apoptosis, ATP levels, glycolytic activity, clonogenic survival, and invasion under both normal and metabolic stress conditions.
PLD1 was significantly overexpressed in SCC compared to adenocarcinoma at mRNA, protein, and enzymatic levels.
Inhibition of PLD1 led to decreased survival rates in SCC cells, while ADC cells showed minimal sensitivity.
Blocking PLD1 reduced glycolytic flux and ATP production and resulted in increased apoptosis under metabolic stress conditions.
PLD1 knockdown negatively affected clonogenic survival and invasion in SCC cells.

Abstract

Abstract Background: Cervical squamous cell carcinoma (SCC) and adenocarcinoma (ADC) are clinically and biologically distinct subtypes, yet the metabolic drivers of SCC aggressiveness remain poorly understood. Phospholipase D1 (PLD1), a lipid-modifying enzyme involved in oncogenic signaling and cancer metabolism, has been reported to be elevated in various malignancies. However, its subtype-specific expression pattern and functional relevance in cervical cancer have not been clearly delineated. Methods: PLD1 expression was evaluated using TCGA datasets and validated in primary cervical tumors by qRT-PCR, PLD activity assays, and immunohistochemistry. Functional studies were performed in primary SCC and ADC cells using shRNA-mediated PLD1 knockdown or a PLD1-selective inhibitor. Apoptosis, ATP levels, glycolytic activity, clonogenic survival, and invasion were measured under basal and metabolic stress conditions. Results: PLD1 was significantly overexpressed in SCC compared with ADC at the mRNA, protein, and enzymatic activity levels. PLD1 inhibition markedly decreased SCC cell survival, whereas ADC cells exhibited minimal sensitivity. PLD1 blockade reduced glycolytic flux and ATP production and increased apoptosis under serum starvation, glucose restriction, and hypoxia. PLD1 knockdown also impaired clonogenic survival and suppressed invasion. These effects were further enhanced by co-treatment with the glycolysis inhibitor 2-deoxy-D-glucose, highlighting a strong dependency of SCC cells on PLD1-mediated metabolic regulation. Conclusions: PLD1 is selectively upregulated in cervical SCC and serves as a key regulator of glycolysis, energy homeostasis, and adaptation to metabolic stress. The pronounced metabolic dependence on PLD1 identifies it as a promising therapeutic target in SCC, and PLD1 inhibition may effectively exploit metabolic vulnerabilities unique to this tumor subtype. Citation Format: Sung Wan Kang, Dong Woo Kang, Yu-na Noh, Young-Jae Lee, Min-Seo Lee, Yong-Man Kim, Shin-Wha Lee. Phospholipase D1 overexpression drives metabolic survival and stress resistance in cervical cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 1275.

Perguntar à IA

Bookmark