Deficiency in STAT1 Signaling Predisposes Gut Inflammation and Prompts Colorectal Cancer Development

Cancers
Sonia A Leon-CabreraLuis I Terrazas

Abstract

Signal transducer and activator of transcription 1 (STAT1) is part of the Janus kinase (JAK/STAT) signaling pathway that controls critical events in intestinal immune function related to innate and adaptive immunity. Recent studies have implicated STAT1 in tumor⁻stroma interactions, and its expression and activity are perturbed during colon cancer. However, the role of STAT1 during the initiation of inflammation-associated cancer is not clearly understood. To determine the role of STAT1 in colitis-associated colorectal cancer (CAC), we analyzed the tumor development and kinetics of cell recruitment in wild-type WT or STAT1-/- mice treated with azoxymethane (AOM) and dextran sodium sulfate (DSS). Following CAC induction, STAT1-/- mice displayed an accelerated appearance of inflammation and tumor formation, and increased damage and scores on the disease activity index (DAI) as early as 20 days after AOM-DSS exposure compared to their WT counterparts. STAT1-/- mice showed elevated colonic epithelial cell proliferation in early stages of injury-induced tumor formation and decreased apoptosis in advanced tumors with over-expression of the anti-apoptotic protein Bcl2 at the colon. STAT1-/- mice showed increased accumulation of Ly6G⁺L...Continue Reading

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Citations

Sep 30, 2020·PloS One·Daniel BodmerSoledad Levano Huaman
Jul 17, 2020·Frontiers in Immunology·Hua-Xing WeiBofeng Li
May 1, 2021·International Journal of Molecular Sciences·Yael Delgado-RamirezSonia Leon-Cabrera
Jul 25, 2021·International Journal of Molecular Sciences·Yael Delgado-RamirezSonia Leon-Cabrera

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Methods Mentioned

BETA
ELISA

Software Mentioned

ZEN lite
ImageJ
Cell Quest
GraphPad Prism

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