These findings suggest that specific environmental pollutants enhance inflammation, cell permeability, and malignant transformation in lung epithelial cells by activating the oncogenic transcription factors STAT3 and NF-κB.
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.
In summary, we demonstrated that fad104 suppressed anchorage-independent growth of melanoma cells, and that the N-terminal region of FAD104 is essential for inhibiting malignant transformation and STAT3 activity.
Blockage of interleukin (IL)-6 or tumor necrosis factor (TNF)-α signaling or inhibition of NF-κB, STAT3, or cyclinD1 expression abrogated the effect of macrophages on malignant transformation in the bionic airway chip culture.
The signal transducer and activator of transcription 3 (STAT3), plays critical roles in malignant transformation and progression and was found to be constitutively activated in a variety of human cancers.
Aberrant activation of Janus kinase-3 (Jak3) and its key down-stream effectors, Signal Transducer and Activator of Transcription-3 (STAT3) and STAT5, is a key feature of malignant transformation in cutaneous T-cell lymphoma (CTCL).
STAT3 contributes to malignant transformation and regulates tumor promoting cytokines, whereas STAT1 is purported to act antagonistically as a tumor suppressor.
Signal transducers and activators of transcription-3 (STAT3), a central cytoplasmic transcription factor, is frequently overexpressed and constitutively activated during malignant transformation.
Moreover, studies utilizing genetic and pharmacological approaches to modulate constitutive STAT3 activity have provided compelling evidence for the critical role of aberrant STAT3 activity in malignant transformation and tumor progression, and thereby validated STAT3 as a novel cancer drug target.
Signal transducers and activators of transcription-3 (STAT3), a central cytoplasmic transcription factor, is frequently overexpressed and constitutively activated by tyrosine during malignant transformation.
Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated in diverse human tumors and may play a direct role in malignant transformation.
Constitutive activation of signal transducer and activator of transcription 3 (STAT3) has been implicated in regulation of growth and malignant transformation.
In conclusion, constitutively activated Stat3 is found to mediate a spontaneous IL-5 production and regulate IL-13 production in CTCL cell lines, pointing toward a new role of Stat3 in malignant transformation.
Constitutive activation of Stat-3 recently has been observed in many tumor cells, and dysregulation of the Stat signaling pathway has been proposed to be implicated in malignant transformation.
The transforming capacity of constitutively activated STAT3 and STAT5 mutants strongly supports their fundamental role in the process of malignant transformation in hematopoietic cells.