Proline Dehydrogenase (PRODH) Is Expressed in Lung Adenocarcinoma and Modulates Cell Survival and 3D Growth by Inducing Cellular Senescence

The identification of markers for early diagnosis, prognosis, and improvement of therapeutic options represents an unmet clinical need to increase survival in Non-Small Cell Lung Cancer (NSCLC), a neoplasm still characterized by very high incidence and mortality. Here, we investigated whether prolin...

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Published in:	International journal of molecular sciences Vol. 25; no. 2; p. 714
Main Authors:	Grossi, Sarah, Berno, Elena, Chiofalo, Priscilla, Chiaravalli, Anna Maria, Cinquetti, Raffaella, Bruno, Antonino, Palano, Maria Teresa, Gallazzi, Matteo, La Rosa, Stefano, Sessa, Fausto, Acquati, Francesco, Campomenosi, Paola
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-01-2024
Subjects:	adenocarcinoma cell lines Adenocarcinoma of Lung - genetics Amino acids Analog to digital converters Apoptosis Autophagy Biotechnology industry Breast cancer Carcinoma, Non-Small-Cell Lung - genetics Cell Survival - genetics cell-based assays cellular senescence Cellular Senescence - genetics Cloning Dehydrogenases Development and progression Growth Health aspects Humans immunohistochemical analysis Immunohistochemistry Lung cancer Lung cancer, Non-small cell Lung Neoplasms - genetics Medical prognosis Metabolism Mortality Mutation Prognosis Proline proline dehydrogenase Proline Oxidase - genetics Proteins Reactive Oxygen Species Tumorigenesis Tumors United States United States lung cancer cell-based assays proline dehydrogenase cellular senescence immunohistochemical analysis adenocarcinoma cell lines
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Summary:	The identification of markers for early diagnosis, prognosis, and improvement of therapeutic options represents an unmet clinical need to increase survival in Non-Small Cell Lung Cancer (NSCLC), a neoplasm still characterized by very high incidence and mortality. Here, we investigated whether proline dehydrogenase (PRODH), a mitochondrial flavoenzyme catalyzing the key step in proline degradation, played a role in NSCLC tumorigenesis. PRODH expression was investigated by immunohistochemistry; digital PCR, quantitative PCR, immunoblotting, measurement of reactive oxygen species (ROS), and functional cellular assays were carried out. PRODH expression was found in the majority of lung adenocarcinomas (ADCs). Patients with PRODH-positive tumors had better cancer-free specific and overall survival compared to those with negative tumors. Ectopic modulation of PRODH expression in NCI-H1299 and the other tested lung ADC cell lines decreased cell survival. Moreover, cell proliferation curves showed delayed growth in NCI-H1299, Calu-6 and A549 cell lines when PRODH-expressing clones were compared to control clones. The 3D growth in soft agar was also impaired in the presence of PRODH. PRODH increased reactive oxygen species production and induced cellular senescence in the NCI-H1299 cell line. This study supports a role of PRODH in decreasing survival and growth of lung ADC cells by inducing cellular senescence.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms25020714