Articulatin B chain induced dendritic cells maturation and driven type I T helper cells and cytotoxic T cells activation

Lu, Tzu-Li; Sher, Yuh‐Pyng; Chen, Hui-Chen; Cheng, Wei‐Chung; Hsu, Ling-Heng; Chen-Chen, Lee

doi:10.1016/j.lfs.2022.120635

Cited by 3 publications

(1 citation statement)

References 17 publications

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“…RNA sequencing was performed by Genomics Biotech Co., Ltd. (Taipei, Taiwan) as previously described [15]. Briefly, total RNA was extracted by TRIzol Reagent (Invitrogen, Massachusetts, USA), and the quality was measured using an RNA6000 Nano kit on an Agilent 2100 Bioanalyzer (Agilent, California, USA) for further library construction for next-generation sequencing.…”

Section: Rna Sequencing and Analysismentioning

confidence: 99%

ADAM9 drives the immunosuppressive microenvironment by cholesterol biosynthesis-mediated activation of IL6-STAT3 signaling for lung tumor progression

Liu

2024

Am J Cancer Res

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Chronic inflammation associated with lung cancers contributes to immunosuppressive tumor microenvironments, reducing CD8 + T-cell function and leading to poor patient outcomes. A disintegrin and metalloprotease domain 9 (ADAM9) promotes cancer progression. Here, we aim to elucidate the role of ADAM9 in the immunosuppressive tumor microenvironment. A bioinformatic analysis of TIMER2.0 was used to investigate the correlation of ADAM9 and to infiltrate immune cells in the human lung cancer database and mouse lung tumor samples. Flow cytometry, immunohistochemistry, and RNA sequencing (RNA-seq) were performed to investigate the ADAM9mediated immunosuppressive microenvironment. The coculture system of lung cancer cells with immune cells, cytokine array assays, and proteomic approach was used to investigate the mechanism. By analyzing the human LUAD database and the mouse lung cancer models, we showed that ADAM9 was associated with the immunosuppressive microenvironment. Additionally, ADAM9 released IL6 protein from cancer cells to inhibit IL12p40 secretion from dendritic cells, therefore leading to dendritic cell dysfunction and further affecting T-cell functions. Proteomic analysis indicated that ADAM9 promoted cholesterol biosynthesis and increased IL6-STAT3 signaling. Mechanistically, ADAM9 reduced the protein stability of LDLR, resulting in reduced cholesterol uptake and induced cholesterol biosynthesis. Moreover, LDLR reduction enhanced IL6-STAT3 activation. We reveal that ADAM9 has a novel biological function that drives the immunosuppressive tumor microenvironment by linking lung cancer's metabolic and signaling axes. Thus, by targeting ADAM9 an innovative and promising therapeutic opportunity was indicated for regulating the immunosuppression of lung cancer.

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Section: Rna Sequencing and Analysismentioning

confidence: 99%

ADAM9 drives the immunosuppressive microenvironment by cholesterol biosynthesis-mediated activation of IL6-STAT3 signaling for lung tumor progression

Liu

2024

Am J Cancer Res

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The role of dysregulated mRNA translation machinery in cancer pathogenesis and therapeutic value of ribosome-inactivating proteins

Jia,

Yuan,

et al. 2023

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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Appraisal of the anti-diabetic potential of polyphenolic compounds from Viscum combreticola Engl.: In vitro α-glucosidase inhibition, LC-ESI-QTOF-MS coupled to pre-column DPPH antioxidative assay, network pharmacology and molecular docking analysis

Moyo,

Madala

2024

South African Journal of Botany

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Articulatin B chain induced dendritic cells maturation and driven type I T helper cells and cytotoxic T cells activation

Cited by 3 publications

References 17 publications

ADAM9 drives the immunosuppressive microenvironment by cholesterol biosynthesis-mediated activation of IL6-STAT3 signaling for lung tumor progression

ADAM9 drives the immunosuppressive microenvironment by cholesterol biosynthesis-mediated activation of IL6-STAT3 signaling for lung tumor progression

The role of dysregulated mRNA translation machinery in cancer pathogenesis and therapeutic value of ribosome-inactivating proteins

Appraisal of the anti-diabetic potential of polyphenolic compounds from Viscum combreticola Engl.: In vitro α-glucosidase inhibition, LC-ESI-QTOF-MS coupled to pre-column DPPH antioxidative assay, network pharmacology and molecular docking analysis

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