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Updated: Jul 7, 2026
Orthotopic Transplantation of Syngeneic Lung Adenocarcinoma Cells to Study PD-L1 Expression
Published on: January 19, 2019
PED is overexpressed and mediates TRAIL resistance in human non-small cell lung cancer
Ciro Zanca1, Michela Garofalo, Cristina Quintavalle
1Department of Cellular and Molecular Biology and Pathology, Federico II University of Naples, Naples, Italy.
Abstract:
PED (phosphoprotein enriched in diabetes) is a death-effector domain (DED) family member with a broad anti-apoptotic action. PED inhibits the assembly of the death-inducing signalling complex (DISC) of death receptors following stimulation. Recently, we reported that the expression of PED is increased in breast cancer cells and determines the refractoriness of these cells to anticancer therapy. In the present study, we focused on the role of PED in non-small cell lung cancer (NSCLC), a tumour frequently characterized by evasion of apoptosis and drug resistance. Immunohistochemical analysis of a tissue microarray, containing 160 lung cancer samples, indicated that PED was strongly expressed in different lung tumour types. Western blotting performed with specimens from NSCLC-affected patients showed that PED was strongly up-regulated (>6 fold) in the areas of tumour compared to adjacent normal tissue. Furthermore, PED expression levels in NSCLC cell lines correlated with their resistance to tumour necrosis factor related apoptosis-inducing ligand (TRAIL)-induced cell death. The involvement of PED in the refractoriness to TRAIL-induced cell death was investigated by silencing PED expression in TRAIL-resistant NSCLC cells with small interfering (si) RNAs: transfection with PED siRNA, but not with cFLIP siRNA, sensitized cells to TRAIL-induced cell death. In conclusion, PED is specifically overexpressed in lung tumour tissue and contributes to TRAIL resistance.
Insights
Phosphoprotein enriched in diabetes (PED) is overexpressed in non-small cell lung cancer (NSCLC), promoting resistance to apoptosis. Silencing PED sensitizes NSCLC cells to TRAIL-induced death, highlighting its role in lung cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Death Research
Background:
- Phosphoprotein enriched in diabetes (PED) is a DED-family protein with anti-apoptotic functions.
- PED expression is elevated in breast cancer, contributing to therapy resistance.
- Non-small cell lung cancer (NSCLC) often exhibits apoptosis evasion and drug resistance.
Purpose of the Study:
- To investigate the role of PED in non-small cell lung cancer (NSCLC).
- To determine if PED expression correlates with apoptosis evasion and drug resistance in NSCLC.
- To elucidate PED's contribution to resistance against tumor necrosis factor related apoptosis-inducing ligand (TRAIL)-induced cell death.
Main Methods:
- Immunohistochemical analysis of PED expression in 160 lung cancer tissue samples.
- Western blotting to quantify PED up-regulation in NSCLC tumor tissues versus normal tissues.
- Silencing PED expression using small interfering RNAs (siRNAs) in TRAIL-resistant NSCLC cell lines to assess chemosensitivity.
Main Results:
- PED was strongly expressed across various lung tumor types.
- PED was significantly up-regulated (>6 fold) in NSCLC tumor tissues compared to adjacent normal tissues.
- PED expression levels in NSCLC cell lines correlated with resistance to TRAIL-induced apoptosis; PED silencing sensitized cells to TRAIL.
Conclusions:
- PED is specifically overexpressed in lung tumor tissues.
- PED plays a significant role in promoting resistance to TRAIL-induced apoptosis in NSCLC.
- Targeting PED may represent a therapeutic strategy for overcoming TRAIL resistance in lung cancer.
