STAT3 Interactors as Potential Therapeutic Targets for Cancer Treatment

Abstract

Signal transducers and activators of transcription (STATs) mediate essential signaling pathways in different biological processes, including immune responses, hematopoiesis, and neurogenesis. Among the STAT members, STAT3 plays crucial roles in cell proliferation, survival, and differentiation. While STAT3 activation is transient in physiological conditions, STAT3 becomes persistently activated in a high percentage of solid and hematopoietic malignancies (e.g., melanoma, multiple myeloma, breast, prostate, ovarian, and colon cancers), thus contributing to malignant transformation and progression. This makes STAT3 an attractive therapeutic target for cancers. Initial strategies aimed at inhibiting STAT3 functions have focused on blocking the action of its activating kinases or sequestering its DNA binding ability. More recently, the diffusion of proteomic-based techniques, which have allowed for the identification and characterization of novel STAT3-interacting proteins able to modulate STAT3 activity via its subcellular localization, interact with upstream kinases, and recruit transcriptional machinery, has raised the possibility to target such cofactors to specifically restrain STAT3 oncogenic functions. In this article, we summarize the available data about the function of STAT3 interactors in malignant cells and discuss their role as potential therapeutic targets for cancer treatment.

STAT3 expression is correlated with pathological stage in luminal subtypes of breast carcinoma

“…As a result of the studies, STAT types have been found to have special functions (13). It has been reported that a large number of tumors are associated with increased activation levels of STATs, in particular with STAT3 and STAT5 (14)(15)(16)(17). In studies conducted on breast carcinomas, STAT activation has been shown to be associated with invasive breast carcinoma, not with benign and in situ carcinoma (18).…”

Nobiletin, a citrus polymethoxyflavone, enhances the effects of bicalutamide on prostate cancer cellsviadown regulation of NF-κB, STAT3, and ERK activation

“…32 Study show that STAT3 becomes persistently activated in a high percentage of solid and hematopoietic malignancies. 39 NBT exhibited activity of inhibit cancer cells viability, migration and angiogenesis via regulating STAT3 expression. 40,41 Besides, the interaction between STAT3 and NF-kB plays a crucial role in the tumorigenesis, 32 targeting STAT3 and NF-kB offer new chemotherapeutic approaches.…”

In Silico Genetics: Identification of pathogenic nsSNPs in human STAT3 gene associated with Job’s syndrome

“…breast, prostate, ovarian, and colon cancers), thus contributing to malignant transformation and progression which makes STAT3 an attractive therapeutic target for cancers. [57]there is also an evidence that studying gene expression of STAT1 , STAT2 and STAT3 gene can be useful for evaluating the efficacy of IFN treatment of the MS patients . [58] Our study is the first in silico analysis which based on functional and structural analysis while all other previous studies based on in vivo analysis, molecular analysis and genome sequencing [53,[59][60][61] This study revealed eleven Novel Pathological mutations have a potential functional impact and may thus be used as diagnostic markers for Job's syndrome.…”