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Published on: January 7, 2019
Negative regulators of STAT3 signaling pathway in cancers
Moli Wu1,2, Danyang Song1, Hui Li1
1College of Pharmacy, Dalian Medical University, Dalian 116044, People's Republic of China.
Abstract:
STAT3 is the most ubiquitous member of the STAT family and involved in many biological processes, such as cell proliferation, differentiation, and apoptosis. Mounting evidence has revealed that STAT3 is aberrantly activated in many malignant tumors and plays a critical role in cancer progression. STAT3 is usually regarded as an effective molecular target for cancer treatment, and abolishing the STAT3 activity may diminish tumor growth and metastasis. Recent studies have shown that negative regulators of STAT3 signaling such as PIAS, SOCS, and PTP, can effectively retard tumor progression. However, PIAS, SOCS, and PTP have also been reported to correlate with tumor malignancy, and their biological function in tumorigenesis and antitumor therapy are somewhat controversial. In this review, we summarize actual knowledge on the negative regulators of STAT3 in tumors, and focus on the potential role of PIAS, SOCS, and PTP in cancer treatment. Furthermore, we also outline the STAT3 inhibitors that have entered clinical trials. Targeting STAT3 seems to be a promising strategy in cancer therapy.
Insights
Signal transducer and activator of transcription 3 (STAT3) is crucial in cancer. Negative regulators like PIAS, SOCS, and PTP show potential in cancer treatment, despite some controversies regarding their role.
Area of Science:
- Oncology
- Molecular Biology
- Signal Transduction
Background:
- Signal transducer and activator of transcription 3 (STAT3) is a key regulator of cell proliferation, differentiation, and apoptosis.
- Aberrant STAT3 activation is implicated in the progression of numerous malignant tumors.
- STAT3 is recognized as a promising molecular target for cancer therapy, with inhibition potentially reducing tumor growth and metastasis.
Purpose of the Study:
- To review current knowledge on STAT3 negative regulators in tumors.
- To focus on the therapeutic potential of PIAS, SOCS, and PTP in cancer treatment.
- To outline STAT3 inhibitors currently in clinical trials.
Main Methods:
- Literature review of studies on STAT3 signaling and its regulators.
- Analysis of the role of PIAS, SOCS, and PTP in tumorigenesis and cancer therapy.
- Compilation of data on STAT3 inhibitors in clinical development.
Main Results:
- STAT3 plays a critical role in cancer progression and is a viable therapeutic target.
- Negative regulators of STAT3 signaling, including PIAS, SOCS, and PTP, can impede tumor progression.
- The precise roles of PIAS, SOCS, and PTP in tumorigenesis and therapy are complex and sometimes contradictory.
Conclusions:
- Targeting STAT3 represents a promising strategy for cancer therapy.
- Understanding the dual roles of STAT3 negative regulators is essential for effective treatment development.
- Further research into STAT3 inhibitors and their clinical efficacy is warranted.
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