<i>N</i>‐(4‐hydroxyphenyl)retinamide inhibits breast cancer cell invasion through suppressing NF‐KB activation and inhibiting matrix metalloproteinase‐9 expression

Kang, Hee-Jun; Lee, Minjae; Choi, Kyung Chul; Shin, Dongwoon; Ko, Jesang; Jang, Su-Jin

doi:10.1002/jcb.24159

Cited by 31 publications

(23 citation statements)

References 33 publications

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“…Also, it has been proven as a regulator of MMP-9 to promote tumor invasion and metastasis [29, 30]. In addition, Akt signaling regulates the expression of NF-κB as well as MMP-9 in several cancer cells [20, 21].…”

Section: Discussionmentioning

confidence: 99%

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

et al. 2017

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Renal cell carcinoma (RCC) is known as one of the most lethal malignancies in the urological system because of its high incidence of metastasis. Tetrandrine (Tet), a traditional Chinese herbal medicine, exerts a potent anti-cancer effect in a variety of cancer cells. However, the anti-metastatic effect of Tet and its possible mechanism in RCC is still unclear. The present study revealed that Tet significantly suppressed the migration and invasion of RCC 786-O and 769-P cells in vitro. Mechanistically, the protein levels of matrix metalloproteinases 9 (MMP-9), phosphorylated PI3K, PDK1, Akt and NF-κB were markedly reduced after Tet treatment. Moreover, co-treatment with LY294002 (PI3K inhibitor) could further enhance the Tet-inhibited migration and invasion, and the NF-κB and MMP-9 protein levels were further decreased. Similar results were observed after PDTC (NF-κB inhibitor) co-treatment. Conversely, SC79, an Akt activator, could partially reverse the anti-metastatic effects of Tet, accompanied by the restoration of NF-κB and MMP-9 protein levels. In conclusion, the current results indicated that Tet inhibited migration and invasion of RCC partially by regulating Akt/NF-κB/MMP-9 signaling pathway, suggesting that Tet may be a potential therapeutic candidate against metastatic RCC.

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Section: Discussionmentioning

confidence: 99%

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

et al. 2017

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“…MMPs are critical enzymes that digest basement membrane proteins during migration [36,37], but their function in the netrin signaling pathway remain largely unknown. Interestingly, we found that Ntn-1 uniquely increased MMP-12 expression via NF-kB activation in promoting UCB-MSCs motility.…”

Section: Effect Of Netrin-1 On Human Ucb-msc Motilitymentioning

confidence: 99%

Netrin-1 Induces MMP-12-Dependent E-Cadherin Degradation Via the Distinct Activation of PKCα and FAK/Fyn in Promoting Mesenchymal Stem Cell Motility

Lee

Jung

et al. 2014

Stem Cells and Development

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Netrin-1 (Ntn-1) is a potent inducer of neuronal cell migration; however, its molecular mechanism that guides the migratory behavior of stem cells has not been characterized. In this study, we investigate the role of Ntn-1 in promoting the motility of human umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) and its related signaling pathways. Ntn-1 (50 ng/mL) significantly increased motility of UCB-MSCs, which was inhibited by blocking antibodies for deleted in colorectal cancer (DCC) and integrin (IN) a6b4. Ntn-1 in DCC stimulated protein kinase Ca (PKCa) activation, but not PKCe, PKCy, and PKCz, while Ntn-1 in INa6b4 induced the phosphorylation of focal adhesion kinase (FAK) and Fyn. Notably, Ntn-1 induced phosphorylation of extracellular signal-regulated kinases (ERK), c-Jun N-terminal kinases ( JNK), and nuclear factor kappa-B (NF-kB), but they were concurrently downregulated by blocking the activities of PKCa, FAK, and Fyn. Ntn-1 uniquely increased the MMP-12 expression of all the matrix metalloproteinase (MMP) isoforms present in UCB-MSCs, though this was significantly blocked by an NF-kB inhibitor. Finally, Ntn-1 induced the MMP-12-dependent degradation of E-cadherin (E-cad), while Ntn-1 abrogated the interaction between E-cad and p120-catenin. In addition, Ntn-1 has the ability to stimulate cytoskeletal reorganization-related proteins, such as Cdc42, Rac1, Profilin-1, Cofilin-1, a-Actinin-4, and filamentous actin (F-actin) in UCB-MSCs. These results demonstrate that Ntn-1 induces MMP-12-dependent E-cad degradation via the distinct activation of PKCa and FAK/Fyn, which is necessary to govern the activation of ERK, JNK, and NF-kB in promoting motility of UCBMSCs.

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“…Involvement in metastasis has been implicated in all of these pathways. NF-kappa B has been shown to be important for promoting migration and metastasis [10] and upregulating the expression of matrix metalloproteinases, urokinase-type plasminogen activator, and cytokines in highly metastatic cancer cell lines [11-13]. In contrast, although JNK is important in inflammation, proliferation, and apoptosis, it also regulates cell migration by maintaining the labile adhesions required for rapid cell migration [14,15].…”

Section: Introductionmentioning

confidence: 99%

Receptor-interacting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways

et al. 2014

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IntroductionMetastasis is the main cause of breast cancer morbidity and mortality. Processes that allow for tumor cell migration and invasion are important therapeutic targets. Here we demonstrate that receptor-interacting protein kinase 2 (RIP2), a kinase known to be involved in inflammatory processes, also has novel roles in cancer cell migration and invasion.MethodsA total of six breast cancer expression databases, including The Cancer Genome Atlas, were assessed for RIP2 expression among various clinical subtypes and its role as a prognostic biomarker. mRNA fluorescence in situ hybridization (FISH) for RIP2 was performed on 17 stage III breast cancers to determine if there was a correlation between RIP2 expression and lymph node involvement. RNA-interference was used to knock-down RIP2 expression in MDA-MB-231, Htb126, SUM149PT, MCF7, T47D, and HCC1428 cells. Cell migration and invasion were measured in vitro by scratch/wound healing and transwell migration assays. A xenograft mouse model was used to assess tumor growth and chemosensitivity to docetaxel in vivo in MDA-MB-231 cells with and without RIP2 small hairpin RNA knockdown. Western blot and immunofluorescence imaging were used to evaluate protein expressions.ResultsInterrogation of expression databases showed that RIP2 expression is significantly over-expressed in triple-negative breast cancers (TNBC: estrogen-receptor (ER) negative, progesterone-receptor (PR) negative, Her2/neu- (Her2) negative), compared to other clinical subtypes. High RIP2 expression correlates with worse progression-free survival using a combined breast cancer expression array dataset consisting of 946 patients. Multivariate analysis shows RIP2 as an independent prognostic biomarker. Knock-down of RIP2 significantly decreases migration in both scratch/wound healing and transwell migration assays in MDA-MB-231, Htb126, SUM149PT, MCF7, and T47D cells and is correlated with decreased Nuclear Factor-kappaB and c-Jun N-terminal kinase (JNK) activation. Finally, RIP2 knock-down leads to increased sensitivity to docetaxel and decreased tumor mass and lung metastases in a xenograft mouse model.ConclusionThese results highlight RIP2 as a pro-metastasis kinase in patients with advanced breast cancer. These results also illustrate a novel role for this kinase in addition to its known role in inflammation, and suggest that targeting RIP2 may improve outcomes in advanced breast cancer patients, in which it is overexpressed.

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N‐(4‐hydroxyphenyl)retinamide inhibits breast cancer cell invasion through suppressing NF‐KB activation and inhibiting matrix metalloproteinase‐9 expression

Cited by 31 publications

References 33 publications

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

Tetrandrine inhibits migration and invasion of human renal cell carcinoma by regulating Akt/NF-κB/MMP-9 signaling

Netrin-1 Induces MMP-12-Dependent E-Cadherin Degradation Via the Distinct Activation of PKCα and FAK/Fyn in Promoting Mesenchymal Stem Cell Motility

Receptor-interacting protein kinase 2 promotes triple-negative breast cancer cell migration and invasion via activation of nuclear factor-kappaB and c-Jun N-terminal kinase pathways

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