Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma.
In: Molecular Medicine, Jg. 28 (2022-12-01), Heft 1, S. 1-14
Online
academicJournal
Zugriff:
Background: Diffuse large B cell lymphoma (DLBCL) is an aggressive and molecularly heterogeneous non-Hodgkin’s lymphoma. The B cell receptor (BCR) signaling pathway in DLBCL emerges as a new drug target. Protein phosphatase SHP-1 negatively regulates several oncogenic tyrosine kinases and plays a tumor suppressive role. Methods: The direct SHP-1 agonists were used to evaluate the potential therapeutic implication of SHP-1 in DLBCL. Immunohistochemical staining for SHP-1 was quantified by H-score. The SHP-1 phosphatase activity was determined using tyrosine phosphatase assay. In vitro studies, including MTT, western blot analysis and cell apoptosis, were utilized to examined biological functions of SHP-1. Results: Oral administration of SHP-1 agonist showed the potent anti-tumor effects compared to a selective Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib in mice bearing U2932 xenografts. SHP-1 agonist increased SHP-1 activity as well as downregulated p-Lyn in vivo. Here, we demonstrated that immunohistochemical staining for SHP-1 expression was positive in 76% of DLBCL samples. SHP-1 agonist exerted anti-proliferative and apoptotic effects compared with ibrutinib in DLBCL cells. Mechanistically, SHP-1 agonist decreased BCR signaling, especially p-Lyn, and led to apoptosis. Conclusions: These data suggest that SHP-1 negatively regulates phosphorylation of Lyn, and targeting SHP-1/p-Lyn using SHP-1 agonist has therapeutic potential for treatment of DLBCL. [ABSTRACT FROM AUTHOR]
Titel: |
Interfering B cell receptor signaling via SHP-1/p-Lyn axis shows therapeutic potential in diffuse large B-cell lymphoma.
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Autor/in / Beteiligte Person: | Chen, Ji-Lin ; Chu, Pei-Yi ; Huang, Chun-Teng ; Huang, Tzu-Ting ; Wang, Wan-Lun ; Lee, Yu-Hsuan ; Chang, Yuan-Ya ; Dai, Ming-Shen ; Shiau, Chung-Wai ; Liu, Chun-Yu |
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Zeitschrift: | Molecular Medicine, Jg. 28 (2022-12-01), Heft 1, S. 1-14 |
Veröffentlichung: | 2022 |
Medientyp: | academicJournal |
ISSN: | 1076-1551 (print) |
DOI: | 10.1186/s10020-022-00518-0 |
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