PYCR1 regulates TRAIL‑resistance in non‑small cell lung cancer cells by regulating the redistribution of death receptors

You,Chengcheng; He,Jinlan; Cao,Chunyu; Sheng,Deqiao; Wang,Lin; Huang,Zhixian; Zhang,Xiaoling; Yi,Changjun; Sun,Yingming; Huang,Yiling

doi:10.3892/ol.2024.14349

PYCR1 regulates TRAIL‑resistance in non‑small cell lung cancer cells by regulating the redistribution of death receptors

Authors:
- Chengcheng You
- Jinlan He
- Chunyu Cao
- Deqiao Sheng
- Lin Wang
- Zhixian Huang
- Xiaoling Zhang
- Changjun Yi
- Yingming Sun
- Yiling Huang
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Affiliations: Hubei Key Laboratory of Tumor Microenvironment and Immunotherapy, China Three Gorges University, Yichang, Hubei 443002, P.R. China, Department of Obstetrics, Yiling People's Hospital of Yichang City, The First Affiliated Hospital of Hubei Three Gorges Polytechnic, Yichang, Hubei 443002, P.R. China, Department of Histopathology, Yichang Akeman Pathology and Diagnostics Center, Yichang, Hubei 443002, P.R. China, Department of Medical and Radiation Oncology, Affiliated Sanming First Hospital of Fujian Medical University, Sanming, Fujian 365001, P.R. China
Published online on: March 19, 2024 https://doi.org/10.3892/ol.2024.14349
Article Number: 216
Copyright: © You et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Although recombinant human TNF‑related apoptosis‑inducing ligand (TRAIL) protein exhibits antitumor activity in a number of lung and liver cancer cells and tumor‑bearing animals, TRAIL resistance has substantially restricted its clinical application. Pyrroline‑5‑carboxylate reductase 1 (PYCR1) is a key enzyme in the regulation of proline synthesis. PYCR1 is highly expressed in various types of malignant tumor, in which it has been implicated in 5‑fluorouracil resistance. However, the possible relationship between PYCR1 and TRAIL resistance remains unclear. In the present study, both reverse transcription‑quantitative PCR and western blotting were performed. The results indicated that H1299 cells had higher PYCR1 expression levels and were less sensitive to TRAIL compared with the TRAIL‑sensitive cell line, H460. PYCR1 knockdown in H1299 cells increased TRAIL sensitivity, increased the localization of death receptors (DRs) on the cell surface and activated Caspase‑3/8. By contrast, overexpression of PYCR1 in H1299 cells decreased TRAIL sensitivity, reduced the distribution of DRs on the cell surface and suppressed the activation of Caspase‑3/8. Taken together, these results suggested that PYCR1 promoted TRAIL resistance in the non‑small cell lung cancer cell line, H1299, by preventing redistribution of DRs to the plasma membrane. This in turn inhibited TRAIL‑mediated cell apoptosis by reducing the activation of Caspase‑3/8.

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