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1.
Exp Mol Med ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38945960

RESUMO

Serine is a key contributor to the generation of one-carbon units for DNA synthesis during cellular proliferation. In addition, it plays a crucial role in the production of antioxidants that prevent abnormal proliferation and stress in cancer cells. In recent studies, the relationship between cancer metabolism and the serine biosynthesis pathway has been highlighted. In this context, 3-phosphoglycerate dehydrogenase (PHGDH) is notable as a key enzyme that functions as the primary rate-limiting enzyme in the serine biosynthesis pathway, facilitating the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate. Elevated PHGDH activity in diverse cancer cells is mediated through genetic amplification, posttranslational modification, increased transcription, and allosteric regulation. Ultimately, these characteristics allow PHGDH to not only influence the growth and progression of cancer but also play an important role in metastasis and drug resistance. Consequently, PHGDH has emerged as a crucial focal point in cancer research. In this review, the structural aspects of PHGDH and its involvement in one-carbon metabolism are investigated, and PHGDH is proposed as a potential therapeutic target in diverse cancers. By elucidating how PHGDH expression promotes cancer growth, the goal of this review is to provide insight into innovative treatment strategies. This paper aims to reveal how PHGDH inhibitors can overcome resistance mechanisms, contributing to the development of effective cancer treatments.

2.
Sci Rep ; 13(1): 15023, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700026

RESUMO

Immune checkpoint inhibitors (ICIs) are promising agents for treating melanoma. Given that autoimmune skin diseases exhibit hyper immune reaction, investigation of immune cells from autoimmune skin disease is crucial to validate the effectiveness of ICIs in melanoma treatment. We employed multipanel markers to predict the response to immune checkpoint inhibitors by characterizing the gene expression signatures of skin immune cells in systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis (PS). By analyzing single-cell RNA sequencing data from each dataset, T cell gene signatures from autoimmune skin diseases exhibit a complex immune response in tumors that responded to immunotherapy. Based on that CD86 and CD80 provide essential costimulatory signals for T cell activation, we observed that interaction of CD86 signaling has been enhanced in the T cells of patients with SLE, AD, and PS. Our analysis revealed a common increase in CD86 signals from dendritic cells (DCs) to T cells in patients with SLE, AD, and PS, confirming that dendritic cells produce pro-inflammatory cytokines to activate T cells. Thus, we hypothesize that T cell gene signatures from autoimmune skin diseases exhibit a pro-inflammatory response and have the potential to predict cancer immunotherapy. Our study demonstrated that T cell gene signatures derived from inflammatory skin diseases, particularly SLE and PS, hold promise as potential biomarkers for predicting the response to immune checkpoint blockade therapy in patients with melanoma. Our data provide an understanding of the immune-related characteristics and differential gene expression patterns in autoimmune skin diseases, which may represent promising targets for melanoma immunotherapy.


Assuntos
Doenças Autoimunes , Dermatite Atópica , Lúpus Eritematoso Sistêmico , Melanoma , Psoríase , Dermatopatias , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Melanoma/genética , Melanoma/terapia , Doenças Autoimunes/genética , Doenças Autoimunes/terapia , Imunoterapia , Biomarcadores
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