STAT2 Controls Colorectal Tumorigenesis and Resistance to Anti-Cancer Drugs

Chiriac MT, Hracsko Z, Becker C, Neurath M (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Cancers MDPI

Book Volume: 15

Article Number: 5423

Journal Issue: 22

DOI: 10.3390/cancers15225423

Abstract

Colorectal cancer (CRC) is a significant socioeconomic burden in modern society and is accountable for millions of premature deaths each year. The role of signal transducer and activator of transcription 2 (STAT2)-dependent signaling in this context is not yet fully understood, and no therapies targeting this pathway are currently being pursued. We investigated the role of STAT2 in CRC using experimental mouse models coupled with RNA-sequencing (RNA-Seq) data and functional assays with anti-cancer agents in three-dimensional tumoroids. Stat2^−/− mice showed greater resistance to the development of CRC in both inflammation-driven and inflammation-independent experimental CRC models. In ex vivo studies, tumoroids derived from Stat2^−/− mice with the multiple intestinal neoplasia (Min) mutant allele of the adenomatous polyposis coli (Apc) locus exhibited delayed growth, were overall smaller and more differentiated as compared with tumoroids from Apc^Min/+ wildtype (WT) mice. Notably, tumoroids from Apc^Min/+ Stat2^−/− mice were more susceptible to anti-cancer agents inducing cell death by different mechanisms. Our findings clearly indicated that STAT2 promotes CRC and suggested that interventions targeting STAT2-dependent signals might become an attractive therapeutic option for patients with CRC.

Authors with CRIS profile

Mircea-Teodor Chiriac Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Christoph Becker Professur für Molekulare Gastroenterologie Markus Neurath Lehrstuhl für Innere Medizin I

Additional Organisation(s)

Interdisziplinäres Zentrum für Klinische Forschung

Related research project(s)

A078: Smurf2-dependent repression of type I IFN signalling in inflammatory bowel disease and mucosal healing Jan. 1, 2021 - Dec. 31, 2023

How to cite

APA:

Chiriac, M.-T., Hracsko, Z., Becker, C., & Neurath, M. (2023). STAT2 Controls Colorectal Tumorigenesis and Resistance to Anti-Cancer Drugs. Cancers, 15(22). https://doi.org/10.3390/cancers15225423

MLA:

Chiriac, Mircea-Teodor, et al. "STAT2 Controls Colorectal Tumorigenesis and Resistance to Anti-Cancer Drugs." Cancers 15.22 (2023).

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