Chemotherapy-induced cellular senescence promotes stemness of aggressive B-cell non-Hodgkin’s lymphoma via CCR7/ARHGAP18/IKBα signaling activation

Journal for ImmunoTherapy of Cancer, Год журнала: 2025, Номер 13(1), С. e009356 - e009356

Опубликована: Янв. 1, 2025

Background Resistance to existing therapies is a major cause of treatment failure in patients with refractory and relapsed B-cell non-Hodgkin’s lymphoma (r/r B-NHL). Therapy-induced senescence (TIS) one the most important mechanisms drug resistance. Methods This study used single-cell RNA sequencing analyze doxorubicin-induced senescent B-NHL cells. C-C chemokine receptor 7 (CCR7) expression aggressive was assessed using immunohistochemistry flow cytometry. Lentiviral transfection target CCR7 Raji SU-DHL-2 Protein localization visualized through immunofluorescence, while western blotting co-immunoprecipitation were protein interactions. Cell proliferation measured Counting Kit-8 assay, cells detected senescence-associated β-galactosidase staining. The stemness evaluated colony sphere formation assays. Transwell assays cell migration invasion. Finally, inhibitors GS143 Y27632 examine effect IKBα ARHGAP/RhoA inhibition on B-NHL-TIS. Results Here we identified distinct group TIS, composed memory population characterized by strong positive CCR7, which significantly elevated TIS compared normal proliferating autonomously populations. Additionally, upregulated r/r B-NHL, an independent prognostic factor high being strongly associated poor prognosis. In vitro results indicated that CCL21 induced invasion via blocking reduced these Furthermore, B-NHL-TIS regulated exhibited enhanced phenotypic functional features, including upregulation markers, increased colony-forming, invasive migratory capabilities. Mechanistically, reversed characteristics inhibiting activation ARHGAP18/IKBα signaling. Conclusions Together, promotes CCR7/ARHGAP18/IKBα signaling targeting CCR7/ARHGAP18 might overcome chemoresistance acquisition maintenance.

Язык: Английский

C‐X‐C chemokine receptor type 4 promotes tubular cell senescence and renal fibrosis through β‐catenin‐inhibited fatty acid oxidation

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(3)

Опубликована: Янв. 11, 2024

Abstract The prevalence of chronic kidney disease (CKD) is highly increasing. Renal fibrosis a common pathological feature in various CKD. Previous studies showed tubular cell senescence involved the pathogenesis renal fibrosis. However, inducers and underlying mechanisms have not been fully investigated. C‐X‐C motif chemokine receptor 4 (CXCR4), G‐protein‐coupled seven‐span transmembrane receptor, increases plays an important role injury. Whereas, whether CXCR4 could induce detailed studied yet. In this study, we adopted adriamycin nephropathy 5/6 nephrectomy models, cultured line. Overexpression or knockdown was obtained by injection related plasmids. We identified increased injury cells. expressed predominantly epithelial cells co‐localized with adipose differentiation‐related protein (ADRP) as well senescence‐related P16 INK4A . Furthermore, found overexpression greatly induced activation β‐catenin, while inhibited it. also that fatty acid oxidation triggered lipid deposition To inhibit β‐catenin ICG‐001, inhibitor significantly block CXCR4‐suppressed oxidation. Taken together, our results indicate key mediator promotes inducing inhibiting metabolism. Our findings provide new theory for

Язык: Английский