Abstract
Signal Transducer and Activator of Transcription (STAT) pathway is connected upstream with Janus kinases (JAK) family protein and capable of integrating inputs from different signaling pathways. Each family member plays unique functions in signal transduction and crucial in mediating cellular responses to different kind of cytokines. STAT family members notably STAT3 and STAT5 have been involved in cancer progression whereas STAT1 plays opposite role by suppressing tumor growth. Persistent STAT3/5 activation is known to promote chronic inflammation, which increases susceptibility of healthy cells to carcinogenesis. Here, we review the role of STATs in cancers and inflammation while discussing current therapeutic implications in different cancers and test models, especially the delivery of STAT3/5 targeting siRNA using nanoparticulate delivery system.
Highlights
THE ROLE OF Signal Transducer and Activator of Transcription (STATs) FAMILY MEMBERS IN CANCER AND INFLAMMATIONThe first direct link between STAT family proteins and carcinoma in human derived from research works that demonstrate that constitutively activated STAT3 is crucial for the carcinogenesis of head and neck cancer and multiple myeloma cells [1, 2]
Xiong et al transfected the human colorectal cancer cell lines SW1116 and HT29 with STAT5 small interfering RNAs (siRNAs) and the results indicated that STAT5 is involved in promoting cancer cell growth, cell cycle progression, invasion and migration by modifying expression of B-cell lymphoma 2 (Bcl-2), p16, p21, Ecadherin, Vascular Endothelial Growth Factor (VEGF), MMP, and p27 genes in colorectal cancer [72]
In addition to the well-distinguished role of STAT family as transcription factors in causing inflammation and tumorigenesis, we have described various strategies used to regulate STAT3/5 transcription activity either through Janus kinases (JAK)-STAT inhibitor or RNA interference (RNAi)-based targeting system
Summary
The first direct link between STAT family proteins and carcinoma in human derived from research works that demonstrate that constitutively activated STAT3 is crucial for the carcinogenesis of head and neck cancer and multiple myeloma cells [1, 2]. Several natural-derived pharmacological agents have been used to target aberrant JAK/ signaling pathway by diverse mechanism(s) including blockage of upstream tyrosine kinases that can phosphorylate STAT3/5; activation of negative regulators of STAT3/5 signaling cascade; abrogation of STAT3/5 dimerization, acetylation, and DNA binding [26, 122] These natural-derived STAT3/5 inhibitors have exhibited limited efficacy in clinical trials so far, and additional studies are required to clearly establish their utility as a monotherapy or in combination regimens with existing drugs for cancer patients. Solid tumors, advanced malignancies, metastatic cancer Non-small cell lung cancer Crohn’s disease MF PV MPN MF RA
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
