J 2024

Characterization of the AGR2-NPM3 axis uncovers the AGR2 involvement in PD-L1 regulation in colorectal cancer

MARTIŠOVÁ, Andrea; Jakub FAKTOR; Tereza ŠOŠOLÍKOVÁ; Iveta KLEMESOVA; Tamara KOLAROVA et al.

Základní údaje

Originální název

Characterization of the AGR2-NPM3 axis uncovers the AGR2 involvement in PD-L1 regulation in colorectal cancer

Autoři

MARTIŠOVÁ, Andrea; Jakub FAKTOR; Tereza ŠOŠOLÍKOVÁ; Iveta KLEMESOVA; Tamara KOLAROVA; Jitka HOLCAKOVA a Roman HRSTKA

Vydání

Scientific Reports, Nature Research, 2024, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 3.900

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/24:00138419

Organizační jednotka

Přírodovědecká fakulta

EID Scopus

Klíčová slova anglicky

AGR2; NPM3; Colorectal cancer; PD-L1

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 10. 1. 2025 14:54, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Despite extensive research, the molecular role of AGR2 in the progression and metastasis of colorectal cancer (CRC) has not been fully characterized. We used quantitative mass spectrometry (SWATH MS) to identify differentially expressed proteins in paired CRC cell models of the SW480 and SW620 cell lines in response to AGR2 protein level manipulation. Relying on the results from SWATH MS and subsequent immunochemical validation, we selected NMP3 as the top candidate protein associated with AGR2 in CRC tumour cells in our screen. RT‒qPCR and immunochemical analysis confirmed the involvement of AGR2-mediated regulation of NPM3 at the transcriptional and posttranscriptional levels. Since PD-L1 is a constituent of the NPM3 regulatory axis, we aimed to correlate the changes in PD-L1 to the differential expression of AGR2 in our cell models. We found that AGR2 positively regulates PD-L1 levels in both SW480 and SW620 cell lines; additionally, several different CRC patient transcriptome cohorts confirmed the association of AGR2 with PD-L1. Our work reveals a new AGR2-NPM3 regulatory axis and the involvement of AGR2 in the regulation of PD-L1, which paves the way for the association of AGR2 with immune evasion in CRC cells.