Abstract
Signal transducers and activators of transcription or STAT are proteins that consist of various transcription factors that are responsible for activating genes regarding cell proliferation, differentiation, and apoptosis. They commonly activate several cytokine, growth, or hormone factors via the JAK-STAT signaling pathway by tyrosine phosphorylation which are responsible for giving rise to numerous immune responses. Mutations within the Janus-Kinases (JAKs) or the STATs can set off the commencement of various malfunctions of the immune system of the body; carcinogenesis being an inevitable outcome. STATs are known to act as both oncogenes and tumor suppressor genes which makes it a hot topic of investigation. Various STATs related mechanisms are currently being investigated to analyze its potential of serving as a therapeutic base for numerous immune diseases and cancer; a deeper understanding of the molecular mechanisms involved in the signaling pathways can contribute to the same. This review will throw light upon each STAT member in causing cancer malignancies by affecting subsequent signaling pathways and its genetic and epigenetic associations as well as various inhibitors that could be used to target these pathways thereby devising new treatment options. The review will also focus upon the therapeutic advances made in cancers that most commonly affect people and discuss how STAT genes are identified as prognostic markers.
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Abbreviations
- STAT: :
-
Signal transducers and activators of transcription
- JAK: :
-
Janus kinase
- IFN: :
-
Interferon
- DN: :
-
Dominant negative
- EGF: :
-
Epidermal growth factor
- PDGF: :
-
Platelet-derived growth factor
- CSF-1::
-
Colony-stimulating factor 1
- IL: :
-
Interleukin
- BCL: :
-
B-cell lymphoma
- TRADD::
-
Tumor necrosis factor receptor 1-associated death domain protein
- Mdm2::
-
Murine double minute 2
- c-Myc: :
-
Cellular myelocytomatosis oncogene
- MHC: :
-
Major histocompatibility complex
- bFGF: :
-
Basic fibroblast growth factor
- PTEN/Akt: :
-
Phosphatase and tensin homolog deleted on chromosome 10/Ak strain transforming
- HNSCC: :
-
head and neck squamous cell carcinoma
- TRAIL: :
-
TNF-related apoptosis-inducing ligand
- Fra-1: :
-
Fos-related antigen 1
- TF: :
-
Transcription factor
- FBXW7: :
-
F-box/WD repeat-containing protein 7
- EGFR: :
-
Epidermal growth factor receptor
- ISGF3: :
-
Interferon stimulated gene factor 3
- VEGF: :
-
Vascular endothelial growth factor
- MMP 2: :
-
Matrix metalloproteinase-2
- HFIH: :
-
Hexane fraction of I. helenium
- SH2: :
-
Src Homology 2
- HBV: :
-
Hepatitis B virus
- HCC: :
-
Hepatocellular carcinoma
- DC: :
-
Dendritic cells
- NOD: :
-
Nonobese diabetic
- BM: :
-
Bone marrow
- GM-CSF: :
-
Granulocyte–macrophage colony-stimulating factor
- Tyk: :
-
Tyrosine kinase
- SOCS: :
-
Suppressors of cytokine signaling proteins
- CIS: :
-
Cytokine inhibitor Src homology 2-containing protein
- PIAS: :
-
Protein inhibitors of activated STATs
- ABC: :
-
ATP binding cassette
- MCl -1: :
-
Myeloid cell leukemia 1
- CML: :
-
Chronic myelogenous leukemia
- AML: :
-
Acute myelogenous leukemia
- FLT3-IND: :
-
FLT3 internal tandem duplication
- MSM: :
-
Methylsufonylmethane
- HER: :
-
Human epidermal growth factor receptor
- ERK: :
-
Extracellular signal-regulated kinase
- Th: :
-
T helper
- IAP: :
-
Inhibitors of apoptosis proteins
- Cdk: :
-
Cyclin-dependent kinases
- DNMT: :
-
DNA methyltransferases
- PCa: :
-
Prostate cancer
- ADT: :
-
Androgen deprivation therapy
- BRCA1: :
-
Breast Cancer gene 1
- AR: :
-
Androgen receptor
- ATF 3: :
-
Activating transcription factor 3
- NSCLC: :
-
Non small cell lung cancer
- CIN: :
-
Cervical intraepithelial neoplasia
- TNBC: :
-
Triple negative breast cancer
- OC: :
-
Ovarian cancer
- CXCL: :
-
Chemokine ligand
- EOC: :
-
Epithelial ovarian cancer
- JNK: :
-
Jun N-terminal kinase
- PAK: :
-
Serine/threonine-protein kinase
- PPAR: :
-
Peroxisome proliferator-activated receptor
- CRC: :
-
Colorectal cancers
- COX: :
-
Cyclooxygenase
- IL22RA1: :
-
Interleukin 22 receptor, alpha 1
- OS: :
-
Overall survival
- PDK4: :
-
Pyruvate Dehydrogenase Kinase 4
- TCA:
-
Tricarboxylic acid
- RAS:
-
Rat sarcoma
- MAPK:
-
Mitogen-activated protein kinase
- PI3K:
-
Phosphatidylinositol-3-kinase
- AKT:
-
Protein kinase B
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Acknowledgements
We thank Sir C.V. Raman Research Park and Department of Biotechnology of SRM Institute of Science and Technology, Kattankulathur, Chennai, India for providing laboratory space.
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This research was supported by the Science and Engineering Research Board (SERB), Department of Science and Technology (DST), Govt. of India (Sanction Order No. ECR/2016/000965).
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KS contributed to Conceptualization, supervision and funding acquisition; SB, NJ, SK, RR, VT contributed to investigation, data curation, and writing of the original draft; SB, NJ, SK contributed to visualization; GS, SR, KS contributed to reviewing and editing of the manuscript.
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Jill, N., Bhootra, S., Kannanthodi, S. et al. Interplay between signal transducers and activators of transcription (STAT) proteins and cancer: involvement, therapeutic and prognostic perspective. Clin Exp Med 23, 4323–4339 (2023). https://doi.org/10.1007/s10238-023-01198-8
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DOI: https://doi.org/10.1007/s10238-023-01198-8