Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

Zhang, Lianhua; Sha, Jianjun; Yang, Guoliang; Huang, Xiaokang; Jiang, Bo; Huang, Yiran

doi:10.1080/15384101.2017.1312237

Cited by 57 publications

(49 citation statements)

References 58 publications

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“…Extensive studies have demonstrated that the Notch signaling pathway is also critical for EMT in tumorigenesis and fibrogenesis. The overexpression of Notch1‐induced EMT in PC‐3 cells, and claudin‐1 contributed to EMT by the Notch signaling pathway in human bronchial epithelial cells . In addition, Notch and TGF‐β1 generated a reciprocal positive regulatory loop and cooperatively regulated EMT in epithelial ovarian cancer cells, which provided new insight into the mechanism of EMT .…”

Section: Small Molecules Against Emtmentioning

confidence: 99%

“…The overexpression of Notch1-induced EMT in PC-3 cells, and claudin-1 contributed to EMT by the Notch signaling pathway in human bronchial epithelial cells. 180,181 In addition, Notch and TGF-β1 generated a reciprocal positive regulatory loop and cooperatively regulated EMT in epithelial ovarian cancer cells, which provided new insight into the mechanism of EMT. 182 Moreover, miR-34a downregulation induced by hypoxia enhanced EMT via the Notch signaling pathway in tubular epithelial cells, which indicated that the Notch signaling pathway is critical for EMT during fibrosis.…”

Section: Notch Signaling Pathwaymentioning

confidence: 99%

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Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

109

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Tissue fibrosis and cancer both lead to high morbidity and mortality worldwide; thus, effective therapeutic strategies are urgently needed. Because drug resistance has been widely reported in fibrotic tissue and cancer, developing a strategy to discover novel targets for targeted drug intervention is necessary for the effective treatment of fibrosis and cancer. Although many factors lead to fibrosis and cancer, pathophysiological analysis has demonstrated that tissue fibrosis and cancer share a common process of epithelial‐mesenchymal transition (EMT). EMT is associated with many mediators, including transcription factors (Snail, zinc‐finger E‐box‐binding protein and signal transducer and activator of transcription 3), signaling pathways (transforming growth factor‐β1, RAC‐α serine/threonine‐protein kinase, Wnt, nuclear factor‐kappa B, peroxisome proliferator‐activated receptor, Notch, and RAS), RNA‐binding proteins (ESRP1 and ESRP2) and microRNAs. Therefore, drugs targeting EMT may be a promising therapy against both fibrosis and tumors. A large number of compounds that are synthesized or derived from natural products and their derivatives suppress the EMT by targeting these mediators in fibrosis and cancer. By targeting EMT, these compounds exhibited anticancer effects in multiple cancer types, and some of them also showed antifibrotic effects. Therefore, drugs targeting EMT not only have both antifibrotic and anticancer effects but also exert effective therapeutic effects on multiorgan fibrosis and cancer, which provides effective therapy against fibrosis and cancer. Taken together, the results highlighted in this review provide new concepts for discovering new antifibrotic and antitumor drugs.

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Section: Small Molecules Against Emtmentioning

confidence: 99%

Section: Notch Signaling Pathwaymentioning

confidence: 99%

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Feng

Chen

Vaziri

et al. 2019

Medicinal Research Reviews

109

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“…To assess the transcriptional levels and activities of hMnSOD isoforms in distinct tumor cells, QPCR and MnSOD activity assays were performed. The results of QPCR indicated that the mRNA level of hMnSODa/b expressed higher in HepG‐2, PC‐3, MCF‐7, and 95‐D cells, which displayed strong metastatic ability (Zhao et al, ; Zhang et al, ). Several poorly metastatic tumor cells such as Hela, A549, and K562 cells were detected to show lower transcription of hMnSODa/b (Figure A).…”

Section: Resultsmentioning

confidence: 99%

The novel truncated isoform of human manganese superoxide dismutase has a differential role in promoting metastasis of lung cancer cells

Yang

Shen

et al. 2018

Cell Biology International

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Growing evidences have demonstrated alternative splicing makes great contribution to tumor metastasis since multiple protein isoforms from a single gene that often display different functions in the cell. Human manganese superoxide dismutase (hMnSOD) was revealed dysregulation in progress of tumor metastasis, while the effect of hMnSOD isoforms on metastasis remained unclear. In this study, we showed a novel truncated hMnSOD isoform hMnSOD183, which lacked 39 amino acids compared with hMnSOD222. We expressed two hMnSOD protein isoforms in Escherichia coli, respectively, and found that the MnSOD activity of truncated hMnSOD isoform was especially weaker. In 95-D cells, mRNA levels of hMnSOD variants and MnSOD activity were significantly increased than that in A549 cells. Furthermore, the hMnSODc exhibited lower mRNA level than hMnSODa/b in A549 and 95-D cells. Additionally, the effects of two isoforms were assessed about cell invasion, overexpression of hMnSOD222 but not hMnSOD183 promoted 95-D cells metastasis, and hMnSOD knockdown significantly reduced cells invasive behavior. Overexpression of hMnSOD isoforms also caused changes of metastasis associated proteins, such as up-regulation of MMPs, VEGF and Vimentin and down-regulation of E-cadherin. Moreover, overexpression of hMnSOD183 had weaker effect on metastasis related signaling proteins, such as Akt, JNK and IKKβ, compared to hMnSOD222. In conclusion, our study identified that hMnSOD isoforms induced lung cancer cells invasion through Akt-JNK-IKKβ signaling pathways and the hMnSOD183 isoform played a weaker role than hMnSOD222. Characterization of hMnSOD isoforms is useful for future investigation on metastasis of lung cancer cells.

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“…Notch signaling regulates a series of cellular processes (21). Several studies have revealed that Notch pathway is critically involved in the process of EMT (21,23,24). To examine the role of Notch pathway in tobacco smoke-induced EMT, we addressed the relationship between Notch and gastric EMT induced by tobacco smoke.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the Notch pathway has been reported implicated in a majority of cancers for promoting the malignant phenotype by inducing cell proliferation, drug resistance, resistance to apoptosis, invasion and metastasis (22). Several studies have revealed that Notch pathway is critically involved in the process of EMT (21,23,24). Nonetheless, no studies have been done to examine the role of Notch pathway in tobacco smoke-induced gastric EMT.…”

Section: Introductionmentioning

confidence: 99%

β‑carotene reverses tobacco smoke‑induced gastric EMT via Notch pathway in vivo

Lü¹,

Chen²,

Li³

et al. 2018

Oncol Rep

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Tobacco smoke is one of the serious risk factors of gastric cancer. Epithelial‑mesenchymal transition (EMT) has been shown to be associated with the initiation and carcinogenesis of gastric cancer. The role of Notch pathway in regulating tobacco smoke-induced EMT has not been investigated. β‑carotene, a carotenoid present in fruits, vegetables and rice, suppresses cancer progression. In this investigation, we evaluated the regulatory role of Notch pathway in tobacco smoke‑mediated gastric EMT and the preventive effect of β‑carotene using a BALB/c mouse smoking model. Exposure of mice to tobacco smoke reduced levels of epithelial markers, while the expression of mesenchymal markers were increased. We further found that Notch pathway modulated tobacco smoke-triggered EMT in the stomach of mice, as evidenced by these findings that tobacco smoke activated Notch activities, and tobacco smoke induced EMT was reversed by blocking Notch activities with FLI‑06. Moreover, treatment of β‑carotene prevented tobacco smoke‑mediated activation of Notch and EMT changes. Our data suggested that Notch regulate tobacco smoke induced gastric EMT and the protective effects of β‑carotene in vivo. These findings may establish a new mechanism for tobacco smoke-associated gastric tumorigenesis and its chemoprevention.

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Activation of Notch pathway is linked with epithelial-mesenchymal transition in prostate cancer cells

Cited by 57 publications

References 58 publications

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

Small molecule inhibitors of epithelial‐mesenchymal transition for the treatment of cancer and fibrosis

The novel truncated isoform of human manganese superoxide dismutase has a differential role in promoting metastasis of lung cancer cells

β‑carotene reverses tobacco smoke‑induced gastric EMT via Notch pathway in vivo

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