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Commentary

STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context

Unit of Molecular Oncology, Department of Advanced Cancer Research and Diagnostics, Centro di Riferimento Oncologico di Aviano (CRO), IRCCS, National Cancer Institute, 33081 Aviano, Italy
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Int. J. Mol. Sci. 2018, 19(9), 2818; https://doi.org/10.3390/ijms19092818
Received: 3 August 2018 / Revised: 13 September 2018 / Accepted: 16 September 2018 / Published: 18 September 2018
(This article belongs to the Special Issue Advances in Biological Functions of STAT3)
Signal transducer and activator of transcription 3 (STAT3) is responsible for mediating the transcriptional programs downstream of several cytokine, growth factor, and oncogenic stimuli. Its expression and activity are consistently linked to cellular transformation, as well as tumor initiation and progression. Due to this central role, STAT3 is widely considered a good target for anti-cancer therapy; however, the success of these approaches has been, so far, very limited. Notably, on one side, STAT3 is aberrantly active in many breast cancers, on the other, at the physiological level, it is the main mediator of epithelial cell death during post-lactation mammary-gland involution, thus strongly suggesting that its biological functions are highly context-specific. One of the most peculiar features of STAT3 is that it can act both in cell-autonomous and non-cell-autonomous manners, simultaneously modulating the phenotypes of the tumor cells and their microenvironment. Here, we focus on the role of STAT3 in breast cancer progression, discussing the potential contrasting roles of STAT3 activation in the establishment of locally recurrent and distant metastatic disease. Based on the most recent literature, depending on the tumor cell type, the local microenvironment status, and the stage of the disease, either STAT3 activation or inactivation can support disease progression. Accordingly, cancer cells dynamically exploit STAT3 activity to carry out transcriptional programs somehow contrasting and complementary, such as supporting survival and growth, dormancy and awakening, stem cell-like features, and inflammation, immune response, and immune evasion. As a consequence, to achieve clinical efficacy, the conception and testing of anti-STAT3 targeted therapies will need a very careful evaluation of these opposing roles and of the most appropriate tumor context, disease stage and patient population to treat. View Full-Text
Keywords: STAT3; breast cancer; mammary epithelial cells; inflammation; dormancy; mutation; local recurrence; metastasis STAT3; breast cancer; mammary epithelial cells; inflammation; dormancy; mutation; local recurrence; metastasis
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MDPI and ACS Style

Segatto, I.; Baldassarre, G.; Belletti, B. STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context. Int. J. Mol. Sci. 2018, 19, 2818. https://doi.org/10.3390/ijms19092818

AMA Style

Segatto I, Baldassarre G, Belletti B. STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context. International Journal of Molecular Sciences. 2018; 19(9):2818. https://doi.org/10.3390/ijms19092818

Chicago/Turabian Style

Segatto, Ilenia; Baldassarre, Gustavo; Belletti, Barbara. 2018. "STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context" Int. J. Mol. Sci. 19, no. 9: 2818. https://doi.org/10.3390/ijms19092818

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