Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication

Loh, Chin Yap; Arya, Aditya; Naema, Ahmed Fadhil; Wong, Won Fen; Sethi, Gautam; Looi, Chung Yeng

doi:10.3389/fonc.2019.00048

Cited by 271 publications

(206 citation statements)

References 192 publications

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“…Cell transduction and transcription activator 3 (STAT3) is an important member of the signal transduction and transcription activator family. Continuous activation of STAT3 can lead to abnormal cell proliferation and malignant transformation [16,17]. STAT3 gene is located on 17q21.2 gene.…”

Section: Introductionmentioning

confidence: 99%

Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma

Lai

Meng³

et al. 2019

Bioscience Reports

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Objective: To study the association between SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms and risk of human tongue squamous cell carcinoma (TSCC). Methods: Sanger sequencing was used to determine the genotypes of SP1 rs1353058818 and STAT3 rs1053004 loci in 240 TSCC patients and 240 controls. Levels of hsa-miR-149-5p and hsa-miR-21-5p and expression levels of SP1 and STAT3 proteins in tumor tissues and adjacent normal tissues of TSCC patients were ascertained. Results: Carrying the SP1 rs1353058818 locus deletion allele was a high risk factor for TSCC (OR = 2.997, 95% CI: 1.389–6.466, P = 0.003). The STAT3 rs1053004 locus A allele was a protective factor for TSCC (OR = 0.604, 95% CI: 0.460-0.793, P < 0.001). There was a negative correlation between SP1 mRNA and hsa-miR-149-5p in tumor and adjacent normal tissues (r = −0.81, −0.77). The expression of SP1 protein in tumor tissues of the SP1 rs1353058818 locus DD genotype was significantly higher than in tissues of the ID type, and in tissues of type II it was the lowest. STAT3 mRNA was positively correlated with hsa-miR-21-5p in tumor and adjacent normal tissues (r = 0.75, 0.78). The expression level of STAT3 protein in tumor tissues of patients with STAT3 rs1053004 locus GG genotype was significantly higher than in patients with type GA, and it was the lowest in patients with type AA. Conclusion: Polymorphisms in the SP1 rs1353058818 and STAT3 rs1053004 loci are associated with the risk of human TSCC.

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Section: Introductionmentioning

confidence: 99%

Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma

Lai

Meng³

et al. 2019

Bioscience Reports

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“…the STAT3 inhibitors AZD9150 in non-Hodgkin's lymphoma, OPB-51602 in nonsmall-cell lung cancer and napabucasin in advanced colorectal cancer, and the STAT5 inhibitor pioglitazone (added to imatinib) in chronic myeloid leukaemia. [10][11][12][13][14][15] The role of STATs in the human epithelial carcinogenesis has been poorly investigated, but in the era of studies on inhibitors targeting STAT proteins, this topic seems to be worth exploring. Chan et al reported that Stat3 in mice is required for de novo epithelial carcinogenesis, showing that Stat3 is involved in both initiation and promotion of carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

STAT 3, STAT 5A, STAT 5B and STAT 6 proteins are overexpressed in human basal cell carcinoma

et al. 2019

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Summary Background The molecular pathogenesis of basal cell carcinoma (BCC) is still not precisely described and is the subject of ongoing studies. The role of signal transducers and activators of transcription (STATs) in human epithelial carcinogenesis has been poorly investigated, but in the era of studies on inhibitors targeting STAT proteins this topic seems worth exploring. Increased expression of STAT3 in human nonmelanoma skin cancer (NMSC) has been confirmed in a few studies, but to our knowledge, expression of STAT5A, STAT5B and STAT6 in BCC has not been previously evaluated. Aim To measure expression of STAT3, STAT5A, STAT5B and STAT6 expression in different histopathological subtypes of human BCC and its correlation with selected clinical variables. Methods Immunohistochemistry was used to assess 60 BCC tumour specimens [20 superficial (s)BCCs, 20 nodular (n)BCCs and 20 infiltrative (i)BCCs] and to compare with specimens of healthy skin. There was no significant difference in age or sex between the three groups of patients with BCC. As many tumours showed heterogeneity of staining, the H‐score system was applied to calculate the intensity of immunoexpression. Results Expression of STAT3, STAT5A, STAT5B and STAT6 was observed in all histopathological subtypes of BCC, and was stronger than the expression within the adjacent epidermis and also stronger than the expression within the epidermis in the healthy control group. Statistical analysis revealed no significant differences in mean H‐scores calculated for sBCCs, nBCCs and iBCCs. There were no statistically significant associations between STAT3, STAT5A, STAT5B and STAT6 expression and patient sex/age, and tumour size/site. Conclusion Our results confirm a possible role of STATs in the pathogenesis of BCC and should encourage future investigations on the possible therapeutic implications of this finding.

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“…Although an overall mechanism of action was not identified, these studies suggest that STATs may contribute to tumor growth and progression of obesity-related cancers. Based on the roles of STATs in a wide variety of cancer types [93], future studies will likely reveal critical roles of STAT proteins in obesity-related cancers.…”

Section: Stats and Obesity-related Cancersmentioning

confidence: 99%

Latest advances in STAT signaling and function in adipocytes

2020

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Adipocytes and adipose tissue are not inert and make substantial contributions to systemic metabolism by influencing energy homeostasis, insulin sensitivity, and lipid storage. In addition to well-studied hormones such as insulin, there are numerous hormones, cytokines, and growth factors that modulate adipose tissue function. Many endocrine mediators utilize the JAK-STAT pathway to mediate dozens of biological processes, including inflammation and immune responses. JAKs and STATs can modulate both adipocyte development and mature adipocyte function. Of the seven STAT family members, four STATs are expressed in adipocytes and regulated during adipogenesis (STATs 1, 3, 5A, and 5B).

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Signal Transducer and Activator of Transcription (STATs) Proteins in Cancer and Inflammation: Functions and Therapeutic Implication

Cited by 271 publications

References 192 publications

Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma

Association of SP1 rs1353058818 and STAT3 rs1053004 gene polymorphisms with human tongue squamous cell carcinoma

STAT 3, STAT 5A, STAT 5B and STAT 6 proteins are overexpressed in human basal cell carcinoma

Latest advances in STAT signaling and function in adipocytes

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