STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects
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...
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| Format: | Article |
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MDPI AG
2020-06-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/9/6/126 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Milad Ashrafizadeh |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T19:13:30Z |
| format | Article |
| id | doaj.art-d8ad8f71a1c64750b1ac91ed0bbecd47 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-10T19:13:30Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-d8ad8f71a1c64750b1ac91ed0bbecd472023-11-20T03:40:17ZengMDPI AGBiology2079-77372020-06-019612610.3390/biology9060126STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future ProspectsMilad Ashrafizadeh0Ali Zarrabi1Sima Orouei2Vahideh Zarrin3Ebrahim Rahmani Moghadam4Amirhossein Zabolian5Shima Mohammadi6Kiavash Hushmandi7Yashar Gharehaghajlou8Pooyan Makvandi9Masoud Najafi10Reza Mohammadinejad11Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, IranSabanci University Nanotechnology Research and Application Center (SUNUM), 34956 Tuzla, Istanbul, TurkeyDepartment of Genetic Science, Tehran Medical Science Branch, Islamic Azad University, Tehran 1916893813, IranLaboratory for Stem Cell Research, Shiraz University of Medical Sciences, Shiraz 7134814336, IranDepartment of Anatomical sciences, School of Medicine, Student Research Committee, Shiraz University of Medical Sciences, Shiraz 7134814336, IranYoung Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, IranGeneral Practitioner, Kerman University of Medical Sciences, Kerman 7616913555, IranDepartment of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417414418, IranDepartment of Clinical Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, IranInstitute for Polymers, Composites and Biomaterials (IPCB), National Research Council (CNR), 80125 Naples, ItalyRadiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, IranPharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman 7616911319, IranMolecular 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.https://www.mdpi.com/2079-7737/9/6/126signal transducer and activator of transcription 3 (STAT3)gastric cancermicroRNAlong non-coding RNAcancer therapytumor microenvironment |
| spellingShingle | 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 STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects Biology signal transducer and activator of transcription 3 (STAT3) gastric cancer microRNA long non-coding RNA cancer therapy tumor microenvironment |
| title | STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects |
| title_full | STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects |
| title_fullStr | STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects |
| title_full_unstemmed | STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects |
| title_short | STAT3 Pathway in Gastric Cancer: Signaling, Therapeutic Targeting and Future Prospects |
| title_sort | stat3 pathway in gastric cancer signaling therapeutic targeting and future prospects |
| topic | signal transducer and activator of transcription 3 (STAT3) gastric cancer microRNA long non-coding RNA cancer therapy tumor microenvironment |
| url | https://www.mdpi.com/2079-7737/9/6/126 |
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