Přejít k obsahu
Merck

PACSIN1 promotes immunosuppression in gastric cancer by degrading MHC-I.

Acta biochimica et biophysica Sinica (2024-06-03)
Zhu Liu, Xin Li, Ali Muhammad, Qiannan Sun, Qi Zhang, Yang Wang, Yong Wang, Jun Ren, Daorong Wang
ANOTACE

Gastric cancer (GC) is a common gastrointestinal system malignancy. PACSIN1 functions as an oncogene in various cancers. This study aims to investigate the potential of PACSIN1 as a target in GC treatment. Gene expression is determined by RT-qPCR, immunofluorescence staining, and immunohistochemistry assay. FISH is performed to determine the colocalization of PACSIN1 and the major histocompatibility complex (MHC-I). Cytokine release and cell functions are analyzed by flow cytometry. In vivo assays are also conducted. Histological analysis is performed using H&E staining. The results show that PACSIN1 is overexpressed in GC patients, especially in those with immunologically-cold tumors. A high level of PACSIN1 is associated with poor prognosis. PACSIN1 deficiency inhibits autophagy but increases antigen presentation in GC cells. Moreover, PACSIN1 deficiency inhibits the lysosomal fusion and selective autophagy of MHC-I, increases CD8 + T-cell infiltration, and suppresses tumor growth and liver metastasis in vivo. Additionally, PACSIN1 knockout enhances the chemosensitivity of cells to immune checkpoint blockade. In summary, PACSIN1 mediates lysosomal fusion and selective autophagy of MHC-I and suppresses antigen presentation and CD8 + T-cell infiltration, thus inhibiting antitumor immunity in GC.

MATERIÁLY
Číslo produktu
Značka
Popis produktu

Sigma-Aldrich
Monoclonal Anti-β-Actin antibody produced in mouse, clone AC-74, ascites fluid
Sigma-Aldrich
Anti-B2M, (N-terminal) antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-TNFA antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-FOS antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Anti-FOSB antibody produced in rabbit, IgG fraction of antiserum
Sigma-Aldrich
Anti-PACSIN1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-JUND antibody produced in rabbit, affinity isolated antibody