Serpine1 mRNA confers mesenchymal characteristics to the cell and promotes CD8+ T cells exclusion from colon adenocarcinomas

Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, indepen...

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Published inCell death discovery Vol. 10; no. 1; p. 116
Main Authors Polo-Generelo, Salvador, Rodríguez-Mateo, Cristina, Torres, Belén, Pintor-Tortolero, José, Guerrero-Martínez, José A., König, Julian, Vázquez, Jesús, Bonzón-Kulichenco, Elena, Padillo-Ruiz, Javier, de la Portilla, Fernando, Reyes, José C., Pintor-Toro, José A.
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 06.03.2024
Springer Nature B.V
Nature Publishing Group
Subjects
631/250/2161
631/337/384/2568
692/699/67/1504/1885/1393
692/699/67/580/1884
Anoikis
Apoptosis
Binding sites
Biochemistry
Biomedical and Life Sciences
Cancer
CD8 antigen
Cell adhesion & migration
Cell Biology
Cell Cycle Analysis
Cell migration
Colon
Colorectal cancer
Extracellular matrix
Gene expression
Glycolysis
Invasiveness
Life Sciences
Lymphocytes
Lymphocytes T
Metastases
Metastasis
MicroRNAs
Proteinase inhibitors
Proteins
Proteolysis
RNA polymerase
Splicing factors
Stem Cells
Surgery
Therapeutic targets
Tumors
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Summary:Serine protease inhibitor clade E member 1 (SERPINE1) inhibits extracellular matrix proteolysis and cell detachment. However, SERPINE1 expression also promotes tumor progression and plays a crucial role in metastasis. Here, we solve this apparent paradox and report that Serpine1 mRNA per se, independent of its protein-coding function, confers mesenchymal properties to the cell, promoting migration, invasiveness, and resistance to anoikis and increasing glycolytic activity by sequestering miRNAs. Expression of Serpine1 mRNA upregulates the expression of the TRA2B splicing factor without affecting its mRNA levels. Through transcriptional profiling, we found that Serpine1 mRNA expression downregulates through TRA2B the expression of genes involved in the immune response. Analysis of human colon tumor samples showed an inverse correlation between SERPINE1 mRNA expression and CD8+ T cell infiltration, unveiling the potential value of SERPINE1 mRNA as a promising therapeutic target for colon tumors.
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ISSN:2058-7716
2058-7716
DOI:10.1038/s41420-024-01886-8