STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects
Milad Ashrafizadeh,
Ali Zarrabi,
Sima Orouei,
Vahideh Zarrin,
Ebrahim Rahmani Moghadam,
Amirhossein Zabolian,
Shima Mohammadi,
Kiavash Hushmandi,
Yashar Gharehaghajlou,
Pooyan Makvandi,
Masoud Najafi,
Reza Mohammadinejad
Affiliations
Milad Ashrafizadeh
Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran
Ali Zarrabi
Sabanci University Nanotechnology Research and Application Center (SUNUM), 34956 Tuzla, Istanbul, Turkey
Sima Orouei
Department of Genetic Science, Tehran Medical Science Branch, Islamic Azad University, Tehran 1916893813, Iran
Vahideh Zarrin
Laboratory for Stem Cell Research, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
Ebrahim Rahmani Moghadam
Department of Anatomical sciences, School of Medicine, Student Research Committee, Shiraz University of Medical Sciences, Shiraz 7134814336, Iran
Amirhossein Zabolian
Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran
Shima Mohammadi
General Practitioner, Kerman University of Medical Sciences, Kerman 7616913555, Iran
Kiavash Hushmandi
Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417414418, Iran
Yashar Gharehaghajlou
Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran
Pooyan Makvandi
Institute for Polymers, Composites and Biomaterials (IPCB), National Research Council (CNR), 80125 Naples, Italy
Masoud Najafi
Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran
Reza Mohammadinejad
Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 7616911319, Iran
Molecular signaling pathways play a significant role in the regulation of biological mechanisms, and their abnormal expression can provide the conditions for cancer development. The signal transducer and activator of transcription 3 (STAT3) is a key member of the STAT proteins and its oncogene role in cancer has been shown. STAT3 is able to promote the proliferation and invasion of cancer cells and induces chemoresistance. Different downstream targets of STAT3 have been identified in cancer and it has also been shown that microRNA (miR), long non-coding RNA (lncRNA) and other molecular pathways are able to function as upstream mediators of STAT3 in cancer. In the present review, we focus on the role and regulation of STAT3 in gastric cancer (GC). miRs and lncRNAs are considered as potential upstream mediators of STAT3 and they are able to affect STAT3 expression in exerting their oncogene or onco-suppressor role in GC cells. Anti-tumor compounds suppress the STAT3 signaling pathway to restrict the proliferation and malignant behavior of GC cells. Other molecular pathways, such as sirtuin, stathmin and so on, can act as upstream mediators of STAT3 in GC. Notably, the components of the tumor microenvironment that are capable of targeting STAT3 in GC, such as fibroblasts and macrophages, are discussed in this review. Finally, we demonstrate that STAT3 can target oncogene factors to enhance the proliferation and metastasis of GC cells.
