Proline dehydrogenase in cancer: apoptosis, autophagy, nutrient dependency and cancer therapy

Liu, Yating; Mao, Chao; Liu, Shuang; Xiao, Desheng; Shi, Ying; Tao, Yongguang

doi:10.1007/s00726-021-03032-5

Cited by 13 publications

(11 citation statements)

References 106 publications

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“…In most cases, PRODH regulates cancer growth as a tumour suppressor gene. However, recent reports suggested that PRODH may play a tumour‐promoting or anti‐tumour role depending on the environment and cell type 24 . What role PRODH play in MM remains unknown.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent reports suggested that PRODH may play a tumour-promoting or anti-tumour role depending on the environment and cell type. 24 What role PRODH play in MM remains unknown. In this study, we found that proline promotes cell proliferation at supraphysiological levels (100-500 mg/l) in 72 hr and drug resistance is mediated by PRODH, which is downregulated in MM patients compared with HD and links to poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

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Proline promotes proliferation and drug resistance of multiple myeloma by downregulation of proline dehydrogenase

et al. 2023

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Summary Amino acids in the bone marrow microenvironment (BMME) are a critical factor for multiple myeloma (MM) progression. Here, we have determined that proline is elevated in BMME of MM patients and links to poor prognosis in MM. Moreover, exogenous proline regulates MM cell proliferation and drug resistance. Elevated proline in BMME is due to bone collagen degradation and abnormal expression of the key enzyme of proline catabolism, proline dehydrogenase (PRODH). PRODH is downregulated in MM patients, mainly as a result of promoter hypermethylation with high expression of DNMT3b. Thus, overexpression of PRODH suppresses cell proliferation and drug resistance of MM and exhibits therapeutic potential for treatment of MM. Altogether, we identify proline as a key metabolic regulator of MM, unveil PRODH governing MM progression and provide a promising therapeutic strategy for MM treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Proline promotes proliferation and drug resistance of multiple myeloma by downregulation of proline dehydrogenase

et al. 2023

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“…PRODH can catalyze the first step of proline catabolism and has diverse functional roles in regulating pathophysiological processes, including apoptosis, autophagy, cell senescence, and tumorigenesis. In many types of cancer, PRODH acts as oncogene to promote cancer occurrence and progression ( Yating Liu et al, 2021 ). Elia et al found that the upregulation of PRODH supported 3D growth and metastasis, generated ATP, and acted as a drug target in MCF10A BRCA cells ( Elia et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

MDN1 Mutation Is Associated With High Tumor Mutation Burden and Unfavorable Prognosis in Breast Cancer

Hao

et al. 2022

Front. Genet.

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Background: Breast cancer (BRCA) is the most common cancer worldwide and a serious threat to human health. MDN1 mutations have been observed in several cancers. However, the associations of MDN1 mutation with tumor mutation burden (TMB) and prognosis of BRCA have not been investigated.Methods: Genomic, transcriptomic, and clinical data of 973 patients with BRCA from The Cancer Genome Atlas (TCGA) database were analyzed. The clinical attributes of BRCA based on the MDN1 mutation status were assessed by comparing TMB and tumor infiltrating immune cells. Gene ontology analysis and gene set enrichment analysis (GSEA) were conducted to identify the key signaling pathways associated with MDN1 mutation. Moreover, univariate and multivariate Cox regression analyses were performed to assess the association between prognostic factors and survival outcomes. Finally, nomograms were used to determine the predictive value of MDN1 mutation on clinical outcomes in patients with BRCA.Results: MDN1 was found to have a relatively high mutation rate (2.77%). Compared to the MDN1 wild-type patients, the TMB value was significantly higher in MDN1 mutant patients (p < 0.001). Prognostic analysis revealed that MDN1 mutant patients had a worse survival probability than MDN1 wild-type patients (hazard ratio = 2.91; 95% CI:1.07–7.92; p = 0.036). GSEA revealed samples with MDN1 mutation enriched in retinol metabolism, drug metabolism cytochrome P450, glucuronidation, miscellaneous transport, and binding event pathways.Conclusion: MDN1 mutation was found to be associated with high TMB and inferior prognosis, suggesting that MDN1 mutation may play a potential role in prognosis prediction and immunotherapy guidance in BRCA.

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“…10,11 Tumor cells have the capacity to escape programmed cell death, which could also increase invasiveness in the process of tumor growth, boost tumor angiogenesis, and accelerate cell proliferation. 12,13 Additionally, selective induction of apoptosis is one of the most effective anticancer therapies, including targeted therapy, radiotherapy, and chemotherapy. 14 In view of the fact that large-scale public databases comprising gene expression data as well as clinical information are now available, it has become feasible to create a highly accurate prognostic signature.…”

Section: Backg Rou N Dmentioning

confidence: 99%

“…Apoptosis is implicated in a variety of biological as well as pathological mechanisms, including the progression of tumors, oncogenesis, organ and tissue homeostasis, and embryonic growth 10,11 . Tumor cells have the capacity to escape programmed cell death, which could also increase invasiveness in the process of tumor growth, boost tumor angiogenesis, and accelerate cell proliferation 12,13 . Additionally, selective induction of apoptosis is one of the most effective anticancer therapies, including targeted therapy, radiotherapy, and chemotherapy 14 .…”

Section: Introductionmentioning

confidence: 99%

Development and validation of apoptosis‐related signature and molecular subtype to improve prognosis prediction in osteosarcoma patients

Hong

et al. 2022

Clinical Laboratory Analysis

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Background: Previous evidence has shown that apoptosis performs integral functions in the tumorigenesis and development of various tumors. Therefore, this study aimed to establish a molecular subtype and prognostic signature based on apoptosis-related genes (ARGs) to understand the molecular mechanisms and predict prognosis in patients with osteosarcoma. Methods:The GEO and TARGET databases were utilized to obtain the expression levels of ARGs and clinical information of osteosarcoma patients. Consensus clustering analysis was used to explore the different molecular subtypes based on ARGs. GO, KEGG, GSEA, ESTIMATE, and ssGSEA analyses were performed to examine the differences in biological functions and immune characteristics between the distinct molecular subtypes. Then, we constructed an ARG signature by LASSO analysis. The prognostic significance of the ARG signature in osteosarcoma was determined by Kaplan-Meier plotter, Cox regression, and nomogram analyses.Results: Two apoptosis-related subtypes were identified. Cluster 1 had a better prognosis, higher immunogenicity, and immune cell infiltration, as well as a better response to immunotherapy than Cluster 2. We discovered that patients in the high-risk cohort had a lower survival rate than those in the low-risk cohort according to the ARG signature. Furthermore, Cox regression analysis confirmed that a high risk score independently acted as an unfavorable prognostic marker. Additionally, the nomogram combining risk scores with clinical characteristics can improve prediction efficiency. Conclusion:We demonstrated that patients suffering from osteosarcoma may be classified into two apoptosis-related subtypes. Moreover, we developed an ARG prognostic signature to predict the prognosis status of osteosarcoma patients.

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Proline dehydrogenase in cancer: apoptosis, autophagy, nutrient dependency and cancer therapy

Cited by 13 publications

References 106 publications

Proline promotes proliferation and drug resistance of multiple myeloma by downregulation of proline dehydrogenase

Proline promotes proliferation and drug resistance of multiple myeloma by downregulation of proline dehydrogenase

MDN1 Mutation Is Associated With High Tumor Mutation Burden and Unfavorable Prognosis in Breast Cancer

Development and validation of apoptosis‐related signature and molecular subtype to improve prognosis prediction in osteosarcoma patients

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