2026-04-17T04:09:52Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1734672025-12-05T13:15:42Zcom_2072_1057col_2072_478798col_2072_478916col_2072_478917

00925njm 22002777a 4500 dc Santiago, Llipsy author Castro, Marta author Sanz Pamplona, Rebeca author Garzón, Marcela author Ramirez-Labrada, Ariel author Tapia, Elena author Moreno Aguado, Víctor author Layunta, Elena author Gil Gómez, Gabriel author Garrido, Marta author Peña, Raúl author Lanuza, Pilar M. author Comas, Laura author Jaime Sánchez, Paula author Uranga Murillo, Iratxe author Campo, Rosa del author Pelegrin, Pablo author Camerer, Eric author Martínez Lostao, Luis author Muñoz, Guillermo author Uranga, José A. author Alcalde, Anabel author Galvez, Eva M. author Ferrandez, Angel author Bird, Phillip I. author Metkar, Sunil author Arias, Maykel A. author Pardo, Julián author 2021-01-28T12:57:16Z 2021-01-28T12:57:16Z 2020-07-07 2021-01-25T08:11:03Z If not properly regulated, the inflammatory immune response can promote carcinogenesis, as evident in colorectal cancer (CRC). Aiming to gain mechanistic insight into the link between inflammation and CRC, we perform transcriptomics analysis of human CRC, identifying a strong correlation between expression of the serine protease granzyme A (GzmA) and inflammation. In a dextran sodium sulfate and azoxymethane (DSS/AOM) mouse model, deficiency and pharmacological inhibition of extracellular GzmA both attenuate gut inflammation and prevent CRC development, including the initial steps of cell transformation and epithelial-to-mesenchymal transition. Mechanistically, extracellular GzmA induces NF-kappa B-dependent IL-6 production in macrophages, which in turn promotes STAT3 activation in cultured CRC cells. Accordingly, colon tissues from DSS/AOM-treated, GzmA-deficient animals present reduced levels of pSTAT3. By identifying GzmA as a proinflammatory protease that promotes CRC development, these findings provide information on mechanisms that link immune cell infiltration to cancer progression and present GzmA as a therapeutic target for CRC. Càncer colorectal Carcinogènesi Colorectal cancer Carcinogenesis Extracellular Granzyme A Promotes Colorectal Cancer Development by Enhancing Gut Inflammation