Expression of signal transducer and activator of transcription 3 and its phosphorylated form is significantly upregulated in patients with papillary thyroid cancer

Li, Yan; Li, Li; Li, Qinghuai; Wang, Di; Shen, Wei; Zhang, Linlei; Guo, Hao

doi:10.3892/etm.2015.2409

Cited by 12 publications

(11 citation statements)

References 35 publications

(33 reference statements)

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“…A number of reports have revealed that the cytokine-induced activation of STAT3 is associated with the evasion of apoptosis, among other cancer hallmarks [6][7][8]. There is a strong correlation between STAT3 overexpression and the pathogenesis of thyroid cancer, as the dysregulated activation of STAT3 has been reported in human specimens of thyroid cancers [9,10]. Apoptosis, or programmed cell death is an important phenomenon that maintains normal cell proliferation and growth (regulated by a system of interconnected signals that is often dysregulated in most human pathologies, including cancer) [40].…”

Section: Discussionmentioning

confidence: 99%

“…Further, a number of reports have also revealed that the cytokine-induced activation of STAT3 is associated with the evasion of apoptosis, among other cancer hallmarks [6][7][8]. There is a strong correlation between STAT3 overexpression and the pathogenesis of thyroid cancer, as the dysregulated activation of STAT3 has been reported in human specimens of thyroid cancers [9,10].…”

Section: Introductionmentioning

confidence: 99%

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Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway

Khan

Ahmed

Elareer

et al. 2020

IJMS

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The constitutive activation of Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signal transduction is well elucidated in STAT3-mediated oncogenesis related to thyroid cancer and is considered to be a plausible therapeutic target. Hence, we investigated whether curcumin, a natural compound, can target the JAK/STAT3 signaling pathway to induce cytotoxic effects in papillary thyroid cancer (PTC) cell lines (BCPAP and TPC-1) and derived thyroid cancer stem-like cells (thyrospheres). Curcumin suppressed PTC cell survival in a dose-dependent manner via the induction of caspase-mediated apoptosis and caused the attenuation of constitutively active STAT3 (the dephosphorylation of Tyr705–STAT3) without affecting STAT3. Gene silencing with STAT3-specific siRNA showed the modulation of genes associated with cell growth and proliferation. The cotreatment of PTC cell lines with curcumin and cisplatin synergistically potentiated cytotoxic effects via the suppression of JAK/STAT3 activity along with the inhibition of antiapoptotic genes and the induction of proapoptotic genes, and it also suppressed the migration of PTC cells by downregulating matrix metalloproteinases and the inhibition of colony formation. Finally, thyrospheres treated with curcumin and cisplatin showed suppressed STAT3 phosphorylation, a reduced formation of thyrospheres, and the downregulated expression of stemness markers, in addition to apoptosis. The current study’s findings suggest that curcumin synergistically enhances the anticancer activity of cisplatin in PTC cells as well as in cancer stem-like cells by targeting STAT3, which suggests that curcumin combined with chemotherapeutic agents may provide better therapeutic outcomes.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway

Khan

Ahmed

Elareer

et al. 2020

IJMS

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“…The activation of STAT3 leads to the upregulation of MMP2 and VEGFA, thereby enhancing the migration and invasion of tumor cells (36). STAT3 is constitutively activated in numerous types of human cancer, usually by phosphorylation of a conserved tyrosine residue in response to extracellular signals from cytokines and growth factors (45). Activated p-STAT3 forms homo-or heterodimers that translocate into the nucleus and induce the transcription of target genes, including MMP2 and VEGFA.…”

Section: Discussionmentioning

confidence: 99%

Plk1 promotes the migration of human lung adenocarcinoma epithelial cells via STAT3 signaling

Yan

et al. 2018

Oncol Lett

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Polo-like kinase (Plk)1 contributes to the development of human cancer via multiple mechanisms, such as promoting the migration of cancer cells. However, the mechanistic basis for the regulation of cell migration by Plk1 remains unknown. To address this question, the present study investigated the effect of Plk1 inhibition on the migration of human lung adenocarcinoma epithelial A549 cells and the molecular factors involved. A549 cells were treated with the Plk1 inhibitor, BI2536, and cell migration was evaluated with the wound-healing assay. The expression of matrix metallopeptidase (MMP)2, vascular endothelial growth factor (VEGF)A, total and phosphorylated signal transducer and activator of transcription (STAT)3 was assessed by western blotting and reverse transcription-polymerase chain reaction following Plk1 knockdown and/or STAT3 overexpression. The interaction between Plk1 and STAT3 was evaluated by co-immunoprecipitation. The levels of MMP2 and VEGFA were decreased by treatment with Plk1 inhibitor. The phosphorylation of STAT3, which acts upstream of MMP2 and VEGFA, was also decreased by Plk1 knockdown, an effect that was abrogated by STAT3 overexpression. In addition, Plk1 was detected to bind with STAT3 either directly or as part of a complex by co-immunoprecipitation experiments. These results indicated that Plk1 may promote the migration of A549 cells via regulation of STAT3 signaling.

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“…Growing evidence indicates that activated STAT3 participates in angiogenesis regulation, with a critical role 67 . VEGF and bFGF are known to be involved in endothelial cell proliferation, extracellular matrix degradation, endothelial cell migration, and modulation of junctional adhesion molecules; both have been described as the leading mediators of angiogenesis that can be upregulated by activated STAT3 in glioblastoma stem cells 68 , papillary thyroid cancer 69 , and colorectal cancer 70 , thereby promoting the formation of new blood vessels and development of cancer. STAT3 is involved in various aspects of tumor microenvironment to cultivate a favorable environment for cancer development.…”

Section: Pivotal Biological Functions Of Stat3 In Cancermentioning

confidence: 99%

Multiple regulation pathways and pivotal biological functions of STAT3 in cancer

Yuan

Zhang

Niu

2015

Sci Rep

196

148

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STAT3 is both a transcription activator and an oncogene that is tightly regulated under normal physiological conditions. However, abundant evidence indicates that STAT3 is persistently activated in several cancers, with a crucial position in tumor onset and progression. In addition to its traditional role in cancer cell proliferation, invasion, and migration, STAT3 also promotes cancer through altering gene expression via epigenetic modification, inducing epithelial–mesenchymal transition (EMT) phenotypes in cancer cells, regulating the tumor microenvironment, and promoting cancer stem cells (CSCs) self-renewal and differentiation. STAT3 is regulated not only by the canonical cytokines and growth factors, but also by the G-protein-coupled receptors, cadherin engagement, Toll-like receptors (TLRs), and microRNA (miRNA). Despite the presence of diverse regulators and pivotal biological functions in cancer, no effective therapeutic inventions are available for inhibiting STAT3 and acquiring potent antitumor effects in the clinic. An improved understanding of the complex roles of STAT3 in cancer is required to achieve optimal therapeutic effects.

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Expression of signal transducer and activator of transcription 3 and its phosphorylated form is significantly upregulated in patients with papillary thyroid cancer

Cited by 12 publications

References 35 publications

Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway

Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway

Plk1 promotes the migration of human lung adenocarcinoma epithelial cells via STAT3 signaling

Multiple regulation pathways and pivotal biological functions of STAT3 in cancer

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