EZH2 enhances the invasive capability of renal cell carcinoma cells via activation of STAT3
نویسندگان
چکیده
The enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) gene has been recognized to be a proto‑oncogene and to be linked to human malignancies. However, the additional functions of EZH2 in renal cell carcinoma (RCC) are not completely understood. In the present study, a possible role of EZH2 in RCC was identified. EZH2 was demonstrated to promote the cell proliferation and invasion potential of 769‑P cells, and inhibition of EZH2 was demonstrated to prevent these two processes in 786‑O cells. Mechanically, EZH2 was demonstrated to increase the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and upregulate 72 kDa type IV collagenase (MMP‑2) expression. When cells were treated with small interfering RNA targeting STAT3 or Stattic, a specific inhibitor of STAT3, the invasive ability of the cells was decreased and downregulation of MMP‑2 was observed. Based on these results, in the present study it was hypothesized that EZH2 may serve a critical role in the progression of RCC. Its ability to facilitate invasion makes EZH2 a promising target for the management of advanced RCC.
منابع مشابه
Ginkgetin induces apoptosis in 786-O cell line via suppression of JAK2-STAT3 pathway
Objective(s): Renal cell carcinoma (RCC) is insensitive to conventional chemotherapy. Ginkgetin effectively treats several carcinoma cells. However, little is known about effects of Ginkgetin on RCC. In the present study, using 786-O cells, we evaluate whether Ginkgetin exerts anticancer effects against RCC. Materials and Methods: 786-O cells suspended in the medium containing Ginkgetin were c...
متن کاملNaringenin Enhances the Anti-Cancer Effect of Cyclophosphamide against MDA-MB-231 Breast Cancer Cells Via Targeting the STAT3 Signaling Pathway
Naringenin is a natural compound with potential anti-cancer effects against several cancer types. Also, its precise molecular mechanisms regarding tumor growth suppression has not been completely elucidated. In the current study the apoptosis-inducing and anti-proliferative effects of Naringenin together with cyclophosphamide were studied in breast cancer cells and the participation of JAK2/ST...
متن کاملNaringenin Enhances the Anti-Cancer Effect of Cyclophosphamide against MDA-MB-231 Breast Cancer Cells Via Targeting the STAT3 Signaling Pathway
Naringenin is a natural compound with potential anti-cancer effects against several cancer types. Also, its precise molecular mechanisms regarding tumor growth suppression has not been completely elucidated. In the current study the apoptosis-inducing and anti-proliferative effects of Naringenin together with cyclophosphamide were studied in breast cancer cells and the participation of JAK2/ST...
متن کاملEffect of valproic acid on SOCS1, SOCS3, JAK1, JAK2, STAT3, STAT5A, and SOCS5B in hepatocellular carcinoma HepG2 cell line
Background and aim: Aberrant activation of diverse intracellular signaling pathways involved in differentiation, cell growth, apoptosis. These pathways include known oncogenic pathways such as Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway. The JAK/STAT signaling pathway plays an important role in many cellular functions. This pathway can be activated by variou...
متن کاملQuercetin Synergistically Enhances the Anticancer Efficacy of Docetaxel through Induction of Apoptosis and Modulation of PI3K/AKT, MAPK/ERK, and JAK/STAT3 Signaling Pathways in MDA-MB-231 Breast Cancer Cell Line
Docetaxel is widely used in the treatment of metastatic breast cancer. However, its effectiveness is limited due to chemoresistance and its undesirable side effects. The combination of chemotherapeutic agents and natural compounds is an effective strategy to overcome drug resistance and the ensuing inevitable toxicities. Quercetin is a natural flavonoid with strong antioxidant and anticancer ac...
متن کامل