Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application

Yuan, Xun; Wu, Hua; Han, Na; Xu, Hanxiao; Chu, Qian; Yu, Shiying; Chen, Yuan; Wu, Kongming

doi:10.1186/s13045-014-0087-z

Cited by 202 publications

(172 citation statements)

References 118 publications

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“…In NSCLC cells, EMT is attributed to one of key pathways on therapeutic resistance and tumor recurrence, through enhancing the cancer cells to acquire ability of migration, invasion and stem cell like characteristics. 19 The above results support that hesperidin could be valuable as an agent for anti-NSCLC and the next study will be explored effects of hesperidin on NSCLC animals or patients, alone usage or combined usage with other anti-cancer agents.…”

Section: Discussionsupporting

confidence: 53%

Inhibition of hesperidin on epithelial to mesenchymal transition of non-small cell lung cancer cells induced by TGF-Beta1

Yu¹,

Li²,

Ren³

et al. 2016

IJPER

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Transforming growth factor-β1 (TGF-β1) is a known potent inducer causing epithelial to mesenchymal transition(EMT) in some cancers. The present study was to evaluate the effect of hesperidin on EMT of non-small cell lung cancer (NSCLC) in vitro. In this study, A549 cells, a cellular line of non-small cell lung cancer, were used for evaluation of EMT induced by TGF-β1. MTT assay was used to evaluate the effect of hesperidin on cell viability with or without TGF-β1 co-culture. At the same time of TGF-β1 addition or after cellular morphological change by TGF-β1 stimulation, hesperidin was given to cells, respectively. Roundness of cells, E-cadherin, α-SMA, Col-I, MMP-9, TIMP-1 were evaluated EMT by TGF-β1 induction and effect of hesperidin on the transition. 40 and 80μM hesperidin showed significant inhibition on cellular viability without TGF-β1; coculture with TGF-β1, 40μM hesperidin showed significant inhibition on the viability but not showed significant inhibition after TGF-β1 stimulation. Whether co-culture with TGF-β1 or addition after TGF-β1, 40μM hesperidin showed inhibitory effect on epithelial to mesenchymal transition and inhibitory effect on extracellular matrix degradation of MMP-9. The above results suggest that hesperidin could be a potential candidate for inhibited migration of non-small cell lung cancer.

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Section: Discussionsupporting

confidence: 53%

Inhibition of hesperidin on epithelial to mesenchymal transition of non-small cell lung cancer cells induced by TGF-Beta1

Yu¹,

Li²,

Ren³

et al. 2016

IJPER

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“…Non‐small‐cell lung cancer is not only a disease with malignant proliferation but also with high invasiveness and metastasis 3, 4, 5, 7, 23. MiR‐138 has been reported to regulate a number of essential biological progresses 8, 16, 17, 18, 19, 20.…”

Section: Discussionmentioning

confidence: 99%

“…To further understand the regulatory mechanisms of miR‐138 in NSCLC progression, we in this study chose NSCLC A549 and 95‐D cells, of which 95‐D cell is a highly metastatic human NSCLC cell line that is suitable for studying some specific properties of NSCLC, such as EMT 5, 7, 23, 24. First, we examined the effect of miR‐138 on the NSCLC cell growth and found that the overexpression of miR‐138 inhibited cell growth and arrested cell cycle at G0/G1 by suppressing the expression of G‐protein‐coupled receptor kinase‐interacting protein 1 (GIT1).…”

Section: Introductionmentioning

confidence: 99%

MiR‐138 inhibits cell proliferation and reverses epithelial‐mesenchymal transition in non‐small cell lung cancer cells by targeting GIT1 and SEMA4C

Wang

Wen

et al. 2015

J Cellular Molecular Medi

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Non‐small‐cell lung cancer (NSCLC) is one of the most common and lethal malignant tumours worldwide with a poor 5‐year survival rate. Recent studies indicated that miRNAs have been involved in the tumorigenic driver pathways in NSCLC, but the relevant molecular mechanisms are not well‐understood. In this study, we investigated the biological functions and molecular mechanisms of miR‐138 in human NSCLC. The effects of miR‐138 on the NSCLC cell growth and epithelial‐mesenchymal transition (EMT) were first examined. Then the targeting connections of miR‐138 with G‐protein‐coupled receptor kinase‐interacting protein 1 (GIT1) and semaphorin 4C (SEMA4C) were confirmed by dual luciferase reporter assays. Finally, the effects of GIT1 and SEMA4C on the NSCLC cell growth and EMT were investigated respectively. We found that the ectopic expression of miR‐138 resulted in a significant inhibition of NSCLC growth and reversion of EMT. GIT1 and SEMA4C were identified as two novel targets of miR‐138. Furthermore, GIT1 and SEMA4C knockdown inhibited the cell growth and reversed EMT, just like the effects of miR‐138 overexpression on NSCLC cells, whereas ectopic expression of GIT1 and SEMA4C partly rescued the suppressive effects of miR‐138 in NSCLC cells. These data represent a crucial step towards the understanding of the novel roles and molecular mechanism of miR‐138, GIT1 and SEMA4C in NSCLC progression, which may provide some new targets or prognostic biomarkers for NSCLC treatment, thus having implications in translational oncology.

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“…When EMT occurs, epithelial cells gradually transform into mesenchymal-like cells by losing their epithelial-associated functions and characteristics (5). Epigenetic downregulation of E-cadherin expression was observed in advanced NSCLC and restoration of E-cadherin expression strongly suppressed the invasion/migration of tumor cells (6,7). Several signaling pathways are involved in EMT in NSCLC, including TGF-β (8), Slug (9), Wnt/β-catenin/zinc finger E-box binding homeobox 1 signaling (10) and c-Jun N-terminal kinase (JNK) signaling (11).…”

Section: Introductionmentioning

confidence: 99%

miR‑145‑5p inhibits epithelial‑mesenchymal transition via the JNK signaling pathway by targeting MAP3K1 in non‑small cell lung cancer cells

et al. 2017

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Abstract. Lung cancer is one of the most common types of tumors and the leading cause of cancer-associated mortality in the world. Additionally, non-small cell lung cancer (NSCLC) accounts for ~80% of all lung cancer cases. Epithelialmesenchymal transition (EMT) is an important cell biological process, which is associated with cancer migration, metastasis, asthma and fibrosis in the lung. In the present study, it was revealed that miR-145-5p was able to suppress EMT by inactivating the c-Jun N-terminal kinase (JNK) signaling pathway in NSCLC cells. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) was predicted and confirmed to be a novel target of miR-145-5p. Overexpression of MAP3K1 was able to reverse the inhibition of EMT induced by miR-145-5p via the JNK signaling pathway. Overall, the results revealed that miR-145-5p inhibits EMT via the JNK signaling pathway by targeting MAP3K1 in NSCLC cells.

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Notch signaling and EMT in non-small cell lung cancer: biological significance and therapeutic application

Cited by 202 publications

References 118 publications

Inhibition of hesperidin on epithelial to mesenchymal transition of non-small cell lung cancer cells induced by TGF-Beta1

Inhibition of hesperidin on epithelial to mesenchymal transition of non-small cell lung cancer cells induced by TGF-Beta1

MiR‐138 inhibits cell proliferation and reverses epithelial‐mesenchymal transition in non‐small cell lung cancer cells by targeting GIT1 and SEMA4C

miR‑145‑5p inhibits epithelial‑mesenchymal transition via the JNK signaling pathway by targeting MAP3K1 in non‑small cell lung cancer cells

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