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The Duality of STAT2 Mediated Type I Interferon Signaling in the Tumor Microenvironment and Chemoresistance

Overview
Journal Cytokine
Date 2022 Nov 3
PMID 36327541
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Abstract

The tumor microenvironment consists of tumor cells, extracellular matrix, blood vessels, and non-tumor cells such as fibroblasts and immune cells. Crosstalk among components of this cellular ecosystem can transform non-malignant cells and promote tumor invasion and metastasis. Evidence is accumulating that the transcription factor STAT2, a downstream effector of type I interferon (IFN-I) signaling, can either inhibit or promote tumorigenesis depending on the unique environment presented by each type of cancer. STAT2 has long been associated with the canonical JAK/STAT pathway involved in various biological processes including reshaping of the tumor microenvironment and in antitumor immunity. This dichotomous tendency of STAT2 to both inhibit and worsen tumor formation makes the protein a curious, and yet relatively ill-defined player in many cancer pathways involving IFN-I. In this review, we discuss the role of STAT2 in contributing to either a tumorigenic or anti-tumorigenic microenvironment as well as chemoresistance.

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References
1.
Weichselbaum R, Ishwaran H, Yoon T, Nuyten D, Baker S, Khodarev N . An interferon-related gene signature for DNA damage resistance is a predictive marker for chemotherapy and radiation for breast cancer. Proc Natl Acad Sci U S A. 2008; 105(47):18490-5. PMC: 2587578. DOI: 10.1073/pnas.0809242105. View

2.
Cao X, Liang Y, Hu Z, Li H, Yang J, Hsu E . Next generation of tumor-activating type I IFN enhances anti-tumor immune responses to overcome therapy resistance. Nat Commun. 2021; 12(1):5866. PMC: 8497482. DOI: 10.1038/s41467-021-26112-2. View

3.
Dongre A, Weinberg R . New insights into the mechanisms of epithelial-mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2018; 20(2):69-84. DOI: 10.1038/s41580-018-0080-4. View

4.
Wang J, Pham-Mitchell N, Schindler C, Campbell I . Dysregulated Sonic hedgehog signaling and medulloblastoma consequent to IFN-alpha-stimulated STAT2-independent production of IFN-gamma in the brain. J Clin Invest. 2003; 112(4):535-43. PMC: 171394. DOI: 10.1172/JCI18637. View

5.
Johnson D, OKeefe R, Grandis J . Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nat Rev Clin Oncol. 2018; 15(4):234-248. PMC: 5858971. DOI: 10.1038/nrclinonc.2018.8. View