Targeting of cell cycle and let-7a/STAT3 pathway by niclosamide inhibits proliferation, migration and invasion in oral squamous cell carcinoma cells

Li, Xiaoxu; Ding, Ruiyu; Han, Zewen; Ma, Zeyun; Wang, Yixiang

doi:10.1016/j.biopha.2017.09.149

Cited by 26 publications

(22 citation statements)

References 46 publications

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“…Hierarchical bi‐clustering analysis indicated significant gene signatures in TRIB2 High /MAP3K1High GBM compared withTRIB2 Low /MAP3K1Low GBM (Figure A). Additionally, KEGG pathway analysis demonstrated multiple molecular pathways that were related to malignant cancer and therapeutic resistance, including cell cycle pathways and the NOTCH, DNA replication, and p53 pathways. Similar results were observed by gene set enrichment analysis (GSEA) (Figure C,D, and E).…”

Section: Resultsmentioning

confidence: 99%

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

et al. 2019

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Introduction Glioblastoma (GBM) is the most lethal primary malignant brain tumor in adults with poor survival due to acquired therapeutic resistance and rapid recurrence. Currently, the standard clinical strategy for glioma includes maximum surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy; however, the median survival of patients with GBM remains poor despite these comprehensive therapies. Therefore, the identification of new prognostic biomarkers is urgently needed to evaluate the malignancy and long‐term outcome of glioma. Aims To further investigate prognostic biomarkers and potential therapeutic targets for GBM. Results In this study, we identified tribbles pseudokinase 2 (TRIB2) as one of the genes that is most correlated with pathological classification, radioresistance, and TMZ resistance in glioma. Additionally, the expression of mitogen‐activated protein kinase kinase kinase 1 (MAP3K1) showed a strong correlation with TRIB2. Moreover, a combined increase in TRIB2 and MAP3K1 was observed in GBM and indicated a poor prognosis of patients with glioma. Finally, enriched TRIB2 expression and MAP3K1 expression were shown to be associated with resistance to TMZ and radiotherapy. Conclusion Combined elevation of TRIB2 and MAP3K1 could be novel prognostic biomarkers and potential therapeutic targets to evaluate the malignancy and long‐term outcomes of GBM.

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Section: Resultsmentioning

confidence: 99%

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

et al. 2019

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“…Many studies have reported on the niclosamide enhances cytotoxicity on various cancers, including oral cancer, lung cancer, colon, thyroid, cervix, ovarian, kidney, and prostate cancers, via STAT3, EGFR/PI3K/Akt, RANKL Wnt, mTOR, HIF‐1α/VEGF, Ras, c‐myc, and Notch signal pathways and mitochondria dysfunction 11, 12, 13, 14, 26, 27, 28, 29, 30, 31, 32, 33. Cancer cell upregulates other important downstream genes such as STAT3, which contributes to cell proliferation, cell survival, and angiogenesis in many cancers.…”

Section: Discussionmentioning

confidence: 99%

A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway

Chen

Huang

et al. 2018

Cancer Medicine

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The incidence and mortality rate of urological cancers is increasing yearly. Niclosamide has been repurposed as an anti‐cancer drug in recent years. Synthesized derivative of niclosamide was testified for its anti‐cancer activity in urological cancers. MTT assay was used to measure the cytotoxicity effect of niclosamide and its derivatives in urological cancer cell lines. Migratory ability was monitored by scratch migration assay. Apoptosis and cell cycle changes were analyzed by annexin V and PI staining. The apoptosis‐related signal proteins were evaluated by western blotting. T24 had the best drug sensitivity with the lowest IC 50 in niclosamide and B17 treatment than DU145 and Caki‐1 cells. After niclosamide and B17 treatment, the mitotic cells were decreased, but apoptotic bodies and morphology changes were not prominent in T24, Caki‐1, and DU145 cells. The migratory ability was inhibited in niclosamide treatment than control group on Caki‐1 cells and niclosamide and B17 treatment than control group on DU145 cells. Early apoptosis cells were increased after niclosamide and B17 treatment than control group without cell cycle changes in T24, Caki‐1, and DU145 cells. Programmed cell death was activated majorly through PAPR and bcl‐2 in T24 and caspase‐3 in Caki‐1 cells, respectively. Niclosamide and B17 derivative had good ability in inhibition proliferation and migratory ability in T24, Caki‐1, and DU145 cells without prominent morphology and apoptotic body changes. UCC cells are more sensitive to niclosamide and B17 treatment. Early apoptosis was induced after niclosamide and B17 treatment through different mechanisms in T24, Caki‐1, and DU145 cells.

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“…21,22 Due to the close relationship between glucose metabolism and cell proliferation, we speculated that let-7a-5p may inhibit the aerobic glycolysis and proliferation of breast cancer. 21,22 Due to the close relationship between glucose metabolism and cell proliferation, we speculated that let-7a-5p may inhibit the aerobic glycolysis and proliferation of breast cancer.…”

Section: Let-7a-5p Inhibits Aerobic Glycolysis and Proliferation Ofmentioning

confidence: 99%

“…Selective cleavage after PKM transcription was regulated by heterogeneous nuclear ribonucleoprotein (hnRNP)-A1, hnRNP-A2, and polypyrimidine tract binding (PTB). [19][20][21] In this study, we explored the role of let-7a-5p and PKM2 in the aerobic glycolysis of breast cancer cells. [13][14][15] Some of the related studies of Stat3 oncogene have laid a foundation for the interpretation and treatment of breast cancer formation mechanism.…”

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confidence: 99%

PKM2 promotes glucose metabolism through a let‐7a‐5p/Stat3/hnRNP‐A1 regulatory feedback loop in breast cancer cells

Yao

Yuan

et al. 2018

J of Cellular Biochemistry

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Tumor cells metabolize more glucose to lactate in aerobic or hypoxic conditions than normal cells. Pyruvate kinase isoenzyme type M2 (PKM2) is crucial for tumor cell aerobic glycolysis. We established a role for let‐7a‐5p/Stat3/hnRNP‐A1/PKM2 signaling in breast cancer cell glucose metabolism. PKM2 depletion via small interfering RNA (siRNA) inhibits cell proliferation and aerobic glycolysis in breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) promotes upregulation of heterogeneous nuclear ribonucleoprotein (hnRNP)‐A1 expression, hnRNP‐A1 binding to pyruvate kinase isoenzyme (PKM) pre messenger RNA, and the subsequent formation of PKM2. This pathway is downregulated by the microRNA let‐7a‐5p, which functionally targets Stat3, whereas hnRNP‐A1 blocks the biogenesis of let‐7a‐5p to counteract its ability to downregulate the Stat3/hnRNP‐A1/PKM2 signaling pathway. The downregulation of Stat3/hnRNP‐A1/PKM2 by let‐7a‐5p is verified using a breast cancer. These results suggest that let‐7a‐5p, Stat3, and hnRNP‐A1 form a feedback loop, thereby regulating PKM2 expression to modulate glucose metabolism of breast cancer cells. These findings elucidate a new pathway mediating aerobic glycolysis in breast cancers and provide an attractive potential target for breast cancer therapeutic intervention.

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Targeting of cell cycle and let-7a/STAT3 pathway by niclosamide inhibits proliferation, migration and invasion in oral squamous cell carcinoma cells

Cited by 26 publications

References 46 publications

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

Combined elevation of TRIB2 and MAP3K1 indicates poor prognosis and chemoresistance to temozolomide in glioblastoma

A new niclosamide derivatives‐B17 can inhibit urological cancers growth through apoptosis‐related pathway

PKM2 promotes glucose metabolism through a let‐7a‐5p/Stat3/hnRNP‐A1 regulatory feedback loop in breast cancer cells

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