STAT3 and p53: Dual Target for Cancer Therapy

Pham, Thu-Huyen; Park, Hyo-Min; Kim, Jinju; Hong, Jin Tae; Yoon, Do‐Young

doi:10.3390/biomedicines8120637

Cited by 34 publications

(30 citation statements)

References 198 publications

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“…STAT3 inactivation is also associated with ferroptosis. It has been reported that STAT3 inhibits P53 to facilitate tumour progression by binding to the promoter of p53, which is an important regulator of ferroptoss [ 21 , 48 ]. Qiang et al found that increasing the expression of p-STAT3 could alleviate ferroptosis via SLC7A11 in MLE12 cells by regulating SLC7A11 [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

“…Signal transducer and activator of transcription 3 (STAT3) belongs to the STAT family and is a vital transcription factor involved in inflammation and tumour progression [ 20 ]. Classical STAT3 activation involves the phosphorylation of STAT3 at Tyr705 (p-STAT3 (705)), which interacts with and inhibits P53 [ 21 ]. Wang et al discovered that high expression of STAT3 is relevant to increased malignancy and poor prognosis [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Luo

Gao

Zou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a new form of regulated cell death, which is mediated by intracellular iron. Although it is reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, it is unclear whether ferroptosis can be induced by bavachin in osteosarcoma (OS) cells. In this study, we found that bavachin inhibits the viability of MG63 and HOS OS cell lines along with an increase in the ferrous iron level, ROS accumulation, malondialdehyde overexpression, and glutathione depletion. Moreover, iron chelators (deferoxamine), antioxidants (Vit E), and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) reverse bavachin-induced cell death. Bavachin also altered the mitochondrial morphology of OS cells, leading to smaller mitochondria, higher density of the mitochondrial membrane, and reduced mitochondrial cristae. Further investigation showed that bavachin upregulated the expression of transferrin receptor, divalent metal transporter-1, and P53, along with downregulating the expression of ferritin light chain, ferritin heavy chain, p-STAT3 (705), SLC7A11, and glutathione peroxidase-4 in OS cells. More importantly, STAT3 overexpression, SLC7A11 overexpression, and pretreatment with pifithrin-α (P53 inhibitor) rescued OS cell ferroptosis induced by bavachin. The results show that bavachin induces ferroptosis via the STAT3/P53/SLC7A11 axis in OS cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Luo

Gao

Zou

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…P53 is one of tumor suppressor genes that most widely studied in human cancer, and the activation of p53 mainly leads to the inhibition of cancer cells growth and promotes DNA repair and apoptosis, the role is mainly mediated by its transcriptional activity. In tumor cells, accompanied by the activation of the IL-6/STAT3 signaling pathway, phosphorylated STAT3 can bind to the promoter of the p53 gene to inhibit its transcription, thereby blocking the inhibitory effect of p53 on oncogene transcription ( 61 ). Alpha-fetoprotein (AFP) is a single-stranded serum glycoprotein, an important biomarker commonly used in the clinical diagnosis of HCC, it is a specific protein with high expression during the occurrence of liver cancer.…”

Section: The Role Of the Il-6/stat3 Signaling Pathway In The Initiation Of Liver Cancermentioning

confidence: 99%

IL-6/STAT3 Is a Promising Therapeutic Target for Hepatocellular Carcinoma

Lin

et al. 2021

Front. Oncol.

116

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Hepatocellular carcinoma (HCC) is a common malignant tumor of which the occurrence and development, the tumorigenicity of HCC is involving in multistep and multifactor interactions. Interleukin-6 (IL-6), a multifunctional inflammatory cytokine, has increased expression in HCC patients and is closely related to the occurrence of HCC and prognosis. IL-6 plays a role by binding to the IL-6 receptor (IL-6R) and then triggering the Janus kinase (JAK) associated with the receptor, stimulating phosphorylation and activating signal transducer and activator of transcription 3 (STAT3) to initiate downstream signals, participating in the processes of anti-apoptosis, angiogenesis, proliferation, invasion, metastasis, and drug resistance of cancer cells. IL-6/STAT3 signal axes elicit an immunosuppressive in tumor microenvironment, it is important to therapy HCC by blocking the IL-6/STAT3 signaling pathway. Recent, some inhibitors of IL-6/STAT3 have been development, such as S31-201 or IL-6 neutralizing monoclonal antibody (IL-6 mAb), Madindoline A (Inhibits the dimerization of IL-6/IL-6R/gpl30 trimeric complexes), C188-9 and Curcumin (Inhibits STAT3 phosphorylation), etc. for treatment of cancers. Overall, consideration of the IL-6/STAT3 signaling pathway, and its role in the carcinogenesis and progression of HCC will contribute to the development of potential drugs for targeting treatment of liver cancer.

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“…STAT3 is a downstream effector of ALK that plays an important role in promoting cell survival, proliferation, and immune evasion (11). STAT3 exerts anti-apoptotic effects in ALK+ ALCL mainly by upregulating the anti-apoptotic protein B cell lymphoma extra-large (Bcl-xL) and antagonizing the tumor suppressor P53 (12). STAT3-induced expression of transforming growth factor (TGF)-b, interleukin (IL)-10, and programmed death ligand (PD-L1,CD274, B7-H1) creates a tumor-suppressive microenvironment (13)(14)(15).…”

Section: Signaling Pathways In Alk+ Alcl 21 Stat3 Pathwaymentioning

confidence: 99%

Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma

Wang

et al. 2022

Front. Oncol.

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Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase expressed at early stages of normal development and in various cancers including ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), in which it is the main therapeutic target. ALK tyrosine kinase inhibitors (ALK TKIs) have greatly improved the prognosis of ALK+ALCL patients, but the emergence of drug resistance is inevitable and limits the applicability of these drugs. Although various mechanisms of resistance have been elucidated, the problem persists and there have been relatively few relevant clinical studies. This review describes research progress on ALK+ ALCL including the application and development of new therapies, especially in relation to drug resistance. We also propose potential treatment strategies based on current knowledge to inform the design of future clinical trials.

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STAT3 and p53: Dual Target for Cancer Therapy

Cited by 34 publications

References 198 publications

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

IL-6/STAT3 Is a Promising Therapeutic Target for Hepatocellular Carcinoma

Holistic View of ALK TKI Resistance in ALK-Positive Anaplastic Large Cell Lymphoma

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