STAT3 and Its Pathways’ Dysregulation—Underestimated Role in Urological Tumors

Abstract

Nowadays, molecular research is essential for the better understanding of tumor cells’ pathophysiology. The increasing number of neoplasms is taken under ‘the molecular magnifying glass’; therefore, it is possible to discover the complex relationships between cytophysiology and tumor cells. Signal transducer and activator of transcription 3 (STAT3) belongs to the family of latent cytoplasmic transcription factors called STATs, which comprises seven members: STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6. Those proteins play important role in cytokine-activated gene expression by transducing signals from the cell membrane to the nucleus. Abnormal prolonged activation results in tumorigenesis, metastasis, cell proliferation, invasion, migration, and angiogenesis. Inhibition of this transcription factor inhibits the previously mentioned effects in cancer cells, whereas normal cells are not affected. Hence, STAT3 might be a viable target for cancer therapy.

Novel Histopathological Biomarkers in Prostate Cancer: Implications and Perspectives

“…The role of STAT3 overexpression in tumor tissue remains inconclusive. In patients with PCa [ 98 ], as well as with some other urological [ 99 ] and non-urological solid tumors such as ovarian cancer [ 100 ], hepatocellular cancer [ 101 , 102 ], pancreatic cancer [ 103 , 104 ], and renal cell carcinoma [ 105 ], STAT3 overexpression is linked with poor survival. Regarding patients with colorectal cancer [ 106 , 107 , 108 ], lung cancer [ 109 , 110 , 111 , 112 , 113 ], gastric cancer [ 114 , 115 , 116 , 117 ], and melanoma [ 118 , 119 ], the results of studies are ambiguous—STAT3 overexpression is found to be a factor of favorable prognosis in some while being related to poor outcomes in others.…”

Cell-autonomous GP130 activation suppresses prostate cancer development via STAT3/ARF/p53-driven senescence and confers an immune-active tumor microenvironment

“…In search of such biomarkers, aberrant activity of the Glycoprotein 130 kDa (GP130) signaling axis has been identified as a crucial factor in inflammation and carcinogenesis 4,5 . A key downstream mediator of GP130 signaling is the transcription factor Signal transducer and activator of transcription 3 (STAT3) 5 . STAT3 signaling is aberrant in approximately 50% of PCa 6 and plays a tumor microenvironment (TME)-dependent role in cell proliferation, cell survival, angiogenesis and immune evasion [7][8][9] .…”

“…The accuracy of these treatments is often hampered by the lack of reliable biomarkers allowing to distinguish aggressive from non-aggressive tumors 2,3 . In search of such biomarkers, aberrant activity of the Glycoprotein 130 kDa (GP130) signaling axis has been identified as a crucial factor in inflammation and carcinogenesis 4,5 . A key downstream mediator of GP130 signaling is the transcription factor Signal transducer and activator of transcription 3 (STAT3) 5 .…”

ITM2A inhibits the progression of bladder cancer by downregulating the phosphorylation of STAT3

“…Among the six major proteins within the STAT family, STAT3 emerges as a significant member -a latent cytoplasmic transcription factor pivotal in cytokine-activated gene expression [3,4]. Upon, ligand binding to cell surface receptors, STAT3 undergoes phosphorylation, dimerization, and nuclear translocation [5].…”