Stat3 activation in human endometrial and cervical cancers

Chen, Chunliang; Hsieh, Fu Chuan; Lieblein, Jacqueline; Brown, Judith; Chan, Cheeling; Wallace, James A.; Cheng, Gong; Hall, Brett M.; Lin, Jiayuh

doi:10.1038/sj.bjc.6603597

Cited by 153 publications

(129 citation statements)

References 36 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…This was unexpected because in cervical cancer patients in situ the STAT3 activation is weak or absent (10). This is in contrast to other malignancies, where STAT3 is constitutively active and is a considered anti-apoptotic factor (13)(14)(15).…”

Section: Introductionmentioning

confidence: 53%

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

et al. 2018

View full text Add to dashboard Cite

Abstract. Cervical cancer stage-dependent therapies include surgery, chemotherapy, radiotherapy and chemoradiotherapy. Concurrent cisplatin-based chemoradiotherapy (CCRT) is the standard therapy for locally advanced cervical carcinoma (FIGO>IIB), however therapy resistance in a subset of patients is still a major clinical challenge. The present study aimed to analyze the impact of Oncostatin M (OSM) stimulation on CCRT-induced cell death. The present study used cells derived from cervical squamous cell carcinomas (SW756, 808, CaSki and 879) and adenocarcinoma (HeLa). The cervical carcinoma cells were HPV18-positive (HeLa, SW756, 808) or HPV16-positive (CaSki, 879). In addition to the established cell lines HeLa, SW756 and CaSki, the more recently generated cervical cancer cells 808 and 879 were also used. To analyze their radiosensitivity, cells were treated with increasing doses of irradiation (0-8 Gy). To mimic chemotherapy, radiotherapy or CCRT in vitro, the cells were challenged with 0.975 µg/ml cisplatin, irradiated with 6 Gy or a combination. A total of 10 ng/ml OSM was applied for 2 h prior to the respective therapy. The responsiveness toward radiation alone varied among the cervical carcinoma cells. CaSki, 808 and 879 cells were resistant to irradiation up to 8 Gy. OSM pre-treatment sensitized two out of five cell lines (HeLa and 879) to irradiation. Notably, all tested cells were sensitized by OSM for CCRT-treatment, particularly in the less radiosensitive cells. Cell death enhancement was dependent on phosphorylated signal transducer and activator of transcription 3 (STAT3; Tyr705) signaling activation as demonstrated with a dominant-negative version of STAT3 interfering with phosphorylation at Tyr705 (dnSTAT3-Y705F). In conclusion, OSM pre-treatment was able to override resistance to CCRT via the STAT3 signaling pathway.

show abstract

Section: Introductionmentioning

confidence: 53%

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Immunohistochemistry and immunocytochemistry were performed as described earlier, 30 by using an anti-Y705 STAT3 antibody (Biolabs, Cell Signaling technology, Danvers, MA, USA) (dilution 1:50, antigen retrieval with 1 Â citrate buffer pH 6.0, incubation overnight at 41C). The detection of EBV infected cells was carried out using either immunohistochemistry with a monoclonal antibody to LMP-1 (CS1-4, DakoCytomation) or ISH with fluorescein-conjugated EBV (EBER1 and 2) oligonucleotides (DakoCytomation) complementary to nuclear RNA portions of the EBER 1 and 2 genes.…”

Section: Immunohistochemistry Immunocytochemistry and Confocal Micromentioning

confidence: 99%

STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma

et al. 2009

View full text Add to dashboard Cite

Nasal-type natural killer (NK) cell lymphoma is an infrequent aggressive malignant disease with very poor prognosis. We aimed to explore the possible role of the transcription factor STAT3 in the pathophysiology of this malignancy, as it was involved in oncogenesis and chemoresistance. For this, we established and characterized a continuous interleukin 2-dependent NK cell line (MEC04) from a patient with a fatal nasal-type NK-cell lymphoma. Cells harbored poor cytotoxic activity against K562 cells, and spontaneously secreted interferon-c, interleukin-10 and vascular-endothelium growth factor in vitro. STAT3 was phosphorylated in Y705 dimerization residue in MEC04 cells and restricted to the nucleus. Y705 STAT3 phosphorylation involved JAK2, as exposure of cells to AG490 inhibitor inhibited Y705 STAT3 phosphorylation. By using recombinant transducible TAT-STAT3-b (b isoform), TAT-STAT3Y705F (a STAT3 protein mutated on Y705 residue, which prevents STAT3 dimerization) and peptides inhibiting specifically STAT3 dimerization, we inhibited STAT3 phosphorylation and cell growth, with cell death induction. Finally, STAT3 was phosphorylated in Y705 residue in the nuclei of lymphoma cells in eight/nine patients with nasal-type NK/T-cell lymphoma and in YT, another NK cell line. Our results suggest that STAT3 protein has a major role in the oncogenic process of nasal-type NK-cell lymphomas, and may represent a promising therapeutical target.

show abstract

“…Immunostaining was performed as described earlier (Chen et al, 2007). Cleaved-caspase-3 (Asp175) antibody was purchased from Cell Signaling Technologies Inc. (Danvers, MA, USA).…”

Section: Immunofluorescence Staining For Apoptosismentioning

confidence: 99%

LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Sobo

et al. 2009

Br J Cancer

Self Cite

View full text Add to dashboard Cite

Persistent activation of the signal transducer and activator of transcription 3 (STAT3) signalling has been linked to oncogenesis and the development of chemotherapy resistance in glioblastoma and other cancers. Inhibition of the STAT3 pathway thus represents an attractive therapeutic approach for cancer. In this study, we investigated the inhibitory effects of a small molecule compound known as LLL-3, which is a structural analogue of the earlier reported STAT3 inhibitor, STA-21, on the cell viability of human glioblastoma cells, U87, U373, and U251 expressing constitutively activated STAT3. We also investigated the inhibitory effects of LLL-3 on U87 glioblastoma cell growth in a mouse tumour model as well as the impact it had on the survival time of the treated mice. We observed that LLL-3 inhibited STAT3-dependent transcriptional and DNA binding activities. LLL-3 also inhibited viability of U87, U373, and U251 glioblastoma cells as well as induced apoptosis of these glioblastoma cell lines as evidenced by increased poly (ADP-ribose) polymerase (PARP) and caspase-3 cleavages. Furthermore, the U87 glioblastoma tumour-bearing mice treated with LLL-3 exhibited prolonged survival relative to vehicle-treated mice (28.5 vs 16 days) and had smaller intracranial tumours and no evidence of contralateral invasion. These results suggest that LLL-3 may be a potential therapeutic agent in the treatment of glioblastoma with constitutive STAT3 activation.

show abstract

Stat3 activation in human endometrial and cervical cancers

Cited by 153 publications

References 36 publications

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

Oncostatin M treatment increases the responsiveness toward cisplatin‑based chemoradiotherapy in cervical cancer cells in a STAT3‑dependent manner

STAT3 transcription factor is constitutively activated and is oncogenic in nasal-type NK/T-cell lymphoma

LLL-3 inhibits STAT3 activity, suppresses glioblastoma cell growth and prolongs survival in a mouse glioblastoma model

Contact Info

Product

Resources

About