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STAT3 in cancer: A double edged sword
Lidia Avalle1, Annalisa Camporeale1, Andrea Camperi1
1Molecular Biotechnology Center, Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, 10126 Turin, Italy.
Abstract:
The transcription factor signal transducer and activator of transcription (STAT) 3 is activated downstream of cytokines, growth factors and oncogenes to mediate their functions under both physiological and pathological conditions. In particular, aberrant/unrestrained STAT3 activity is detected in a wide variety of tumors, driving multiple pro-oncogenic functions. For that, STAT3 is widely considered as an oncogene and is the object of intense translational studies. One of the distinctive features of this factor is however, its ability to elicit different and sometimes contrasting effects under different conditions. In particular, STAT3 activities have been shown to be either pro-oncogenic or tumor-suppressive according to the tumor aetiology/mutational landscape, suggesting that the molecular bases underlining its functions are still incompletely understood. Here we discuss some of the properties that may provide the bases to explain STAT3 heterogeneous functions, and in particular how post-translational modifications contribute shaping its sub-cellular localization and activities, the cross talk between these activities and cell metabolic conditions, and finally how its functions can control the behaviour of both tumor and tumor microenvironment cell populations.
Insights
Signal transducer and activator of transcription (STAT) 3 is a key factor in cell functions. Its dual role as oncogene or tumor suppressor depends on complex modifications and cellular context.
Area of Science:
- Molecular Biology
- Cellular Biology
- Oncology
Background:
- Signal transducer and activator of transcription (STAT) 3 is activated by cytokines, growth factors, and oncogenes.
- Aberrant STAT3 activity is prevalent in various tumors, promoting cancer progression.
- STAT3 is considered an oncogene and is a focus of translational research.
Purpose of the Study:
- To explore the heterogeneous functions of STAT3 in different cellular contexts.
- To elucidate the molecular mechanisms underlying STAT3's contrasting roles.
- To discuss factors influencing STAT3's pro-oncogenic or tumor-suppressive activities.
Main Methods:
- Review of existing literature on STAT3.
- Analysis of post-translational modifications of STAT3.
- Investigation of STAT3's interaction with cell metabolism.
- Examination of STAT3's role in tumor and microenvironment cells.
Main Results:
- STAT3 exhibits context-dependent functions, acting as either a pro-oncogene or tumor suppressor.
- Post-translational modifications significantly influence STAT3's localization and activity.
- STAT3 activity is intricately linked with cellular metabolic states.
- STAT3 controls the behavior of both tumor cells and their microenvironment.
Conclusions:
- The complex functions of STAT3 are shaped by post-translational modifications, cellular metabolism, and microenvironment interactions.
- Understanding these regulatory mechanisms is crucial for deciphering STAT3's role in cancer.
- Further research is needed to fully comprehend STAT3's dualistic behavior in tumorigenesis.
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