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

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

B7-H1 Antigen*/metabolism ; B7-H1 Antigen*/genetics ; Colorectal Neoplasms*/genetics ; Colorectal Neoplasms*/metabolism ; Colorectal Neoplasms*/pathology ; Gene Expression Regulation, Neoplastic* ; Mucoproteins*/metabolism ; Mucoproteins*/genetics ; Nucleophosmin* ; Oncogene Proteins*/metabolism ; Oncogene Proteins*/genetics ; Proteins*/metabolism ; Proteins*/genetics; Humans ; Cell Line, Tumor ; Nuclear Proteins/metabolism ; Nuclear Proteins/genetics

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.
(© 2024. The Author(s).)

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MMCI, 00209805 MH CZ - DRO; P JAC; reg. no. CZ.02.01.01/00/22_008/0004644 Ministerstvo Školství, Mládeže a Tělovýchovy

Keywords: AGR2; Colorectal cancer; NPM3; PD-L1

0 (AGR2 protein, human)
0 (B7-H1 Antigen)
0 (CD274 protein, human)
0 (Mucoproteins)
0 (Nuclear Proteins)
117896-08-9 (Nucleophosmin)
0 (Oncogene Proteins)
0 (Proteins)
0 (NPM3 protein, human)

Date Created: 20240919 Date Completed: 20240919 Latest Revision: 20240925

20240925

PMC11413233

10.1038/s41598-024-72990-z

39300184