Artikel ; Online: Clinical significance of glycogen synthase kinase 3 (GSK-3) expression and tumor budding grade in colorectal cancer: Implications for targeted therapy.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
2023 Band 167, Seite(n) 115592
Abstract: Introduction: Glycogen synthase kinase 3 (GSK-3) has been proposed as a novel cancer target due to its regulating role in both tumor and immune cells. However, the connection between GSK-3 and immunoevasive contexture, including tumor budding (TB) has ... ...
| Abstract | Introduction: Glycogen synthase kinase 3 (GSK-3) has been proposed as a novel cancer target due to its regulating role in both tumor and immune cells. However, the connection between GSK-3 and immunoevasive contexture, including tumor budding (TB) has not been previously examined. Methods: we investigated the expression levels of total GSK-3 as well as its isoforms (GSK-3β and GSK-3α) and examined their potential correlation with TB grade and the programmed cell death-ligand 1 (PD-L1) in colorectal cancer (CRC) tumor samples. Additionally, we compared the efficacy of GSK-3-inhibition with PD-1/PD-L1 blockade in humanized patient-derived (PDXs) xenografts models of high-grade TB CRC. Results: we show that high-grade (BD3) TB CRC is associated with elevated expression levels of total GSK-3, specifically the GSK-3β isoform, along with increased expression of PD-L1 in tumor cells. Moreover, we define an improved risk stratification of CRC patients based on the presence of GSK-3 Conclusions: our study provides compelling evidence for the clinical significance of GSK-3 expression and TB grade in risk stratification of CRC patients. Moreover, our findings strongly support GSK-3 inhibition as an effective therapy specifically targeting high-grade TB in CRC. |
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| Mesh-Begriff(e) | Humans ; CD8-Positive T-Lymphocytes ; Glycogen Synthase Kinase 3 ; Glycogen Synthase Kinase 3 beta ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor ; Clinical Relevance ; Colorectal Neoplasms/pathology |
| Chemische Substanzen | Glycogen Synthase Kinase 3 (EC 2.7.11.26) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; B7-H1 Antigen ; Programmed Cell Death 1 Receptor |
| Sprache | Englisch |
| Erscheinungsdatum | 2023-09-29 |
| Erscheinungsland | France |
| Dokumenttyp | Journal Article |
| ZDB-ID | 392415-4 |
| ISSN | 1950-6007 ; 0753-3322 ; 0300-0893 |
| ISSN (online) | 1950-6007 |
| ISSN | 0753-3322 ; 0300-0893 |
| DOI | 10.1016/j.biopha.2023.115592 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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