Dickkopf 3 attenuates xanthine dehydrogenase expression to prevent oxidative stress‐induced apoptosis

Qui, Shuang; Kano, Junko; Noguchi, Masayuki

doi:10.1111/gtc.12484

Cited by 11 publications

(13 citation statements)

References 41 publications

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“…The pcDNA3.1‐DKK3‐C‐Flag or mock vector was constructed as reported previously . Briefly, YD‐10B cells were transfected in a stable manner with the pcDNA3.1‐DKK‐3‐Flag or mock vector using LipofectAMINE transfection reagent as prescribed by the manufacturer (Invitrogen, Carlsbad, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The pcDNA3.1-DKK3-C-Flag or mock vector was constructed as reported previously. 27 Briefly, YD-10B cells were transfected in a stable manner with the pcDNA3.1-DKK-3-Flag or mock vector using LipofectAMINE transfection reagent as prescribed by the manufacturer (Invitrogen, Carlsbad, CA, USA). After 48 h of incubation, transfected cells were selected in primary cell culture medium containing 200 μg/mL G418 (Promega, Madison, WI, USA).…”

Section: Generation Of Stable Yd-10b Cells Overexpressing Dkk-3mentioning

confidence: 99%

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Meridianin C inhibits the growth of YD‐10B human tongue cancer cells through macropinocytosis and the down‐regulation of Dickkopf‐related protein‐3

Park

Mahesh

et al. 2018

J Cellular Molecular Medi

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Meridianin C is a marine natural product known for its anti‐cancer activity. At present, the anti‐tumour effects of meridianin C on oral squamous cell carcinoma are unknown. Here, we investigated the effect of meridianin C on the proliferation of four different human tongue cancer cells, YD‐8, YD‐10B, YD‐38 and HSC‐3. Among the cells tested, meridianin C most strongly reduced the growth of YD‐10B cells; the most aggressive and tumorigenic of the cell lines tested. Strikingly, meridianin C induced a significant accumulation of macropinosomes in the YD‐10B cells; confirmed by the microscopic and TEM analysis as well as the entry of FITC‐dextran, which was sensitive to the macropinocytosis inhibitor amiloride. SEM data also revealed abundant long and thin membrane extensions that resemble lamellipodia on the surface of YD‐10B cells treated with meridianin C, pointing out that meridianin C‐induced macropinosomes was the result of macropinocytosis. In addition, meridianin C reduced cellular levels of Dickkopf‐related protein‐3 (DKK‐3), a known negative regulator of macropinocytosis. A role for DKK‐3 in regulating macropinocytosis in the YD‐10B cells was confirmed by siRNA knockdown of endogenous DKK‐3, which led to a partial accumulation of vacuoles and a reduction in cell proliferation, and by exogenous DKK‐3 overexpression, which resulted in a considerable inhibition of the meridianin C‐induced vacuole formation and decrease in cell survival. In summary, this is the first study reporting meridianin C has novel anti‐proliferative effects via macropinocytosis in the highly tumorigenic YD‐10B cell line and the effects are mediated in part through down‐regulation of DKK‐3.

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Section: Methodsmentioning

confidence: 99%

Section: Generation Of Stable Yd-10b Cells Overexpressing Dkk-3mentioning

confidence: 99%

Meridianin C inhibits the growth of YD‐10B human tongue cancer cells through macropinocytosis and the down‐regulation of Dickkopf‐related protein‐3

Park

Mahesh

et al. 2018

J Cellular Molecular Medi

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“…Although DKK3 had been thought to be a “tumor suppressor gene”, like other DKK family genes, recent reports demonstrated that DKK3 expression showed oncogenic effects in certain cancers . Thus, the actual function of DKK3 in tumors has been unclear due to the opposite effects of DKK3 on tumor proliferation according to cell context.…”

Section: Discussionmentioning

confidence: 99%

“…These data suggest that DKK3 may have an additional function other than tumor suppression. Our previous study has demonstrated that DKK3 has a prosurvival function, preventing oxidative stress‐induced apoptosis in certain hepatocellular carcinoma cells . Although DKK3 has received attention as a possible new cancer therapeutic target based on its tumor‐suppressing function in several clinical studies, alterations in its function depending on specific cellular contexts need to be clarified.…”

Section: Introductionmentioning

confidence: 99%

Dickkopf‐related protein 3 promotes cell adhesion and invasion during progression of lung adenocarcinoma

Komori

Kano

Nakano

et al. 2019

Pathology International

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Dickkopf‐related protein 3 (DKK3) is one of the DKK family (DKK1‐4), an evolutionally conserved group of secreted glycoproteins characterized by two distinct cysteine‐rich domains. DKK3 is considered to be a tumor suppressor gene. However, it has been shown that 30–50% of various cancers are DKK3‐positive, suggesting that DKK3 may have an additional function other than tumor suppression. In this study, we focused on lung adenocarcinoma, which is the major histological type of lung cancer. We analyzed the relationship between DKK3 expression and clinicopathological features by immunohistochemistry, using 200 lung adenocarcinoma specimens. We found that 40.5% and 59.5% of cases were DKK3‐positive and ‐negative, respectively, and that positive cases had a greater tendency for progression than negative cases (P < 0.05). Furthermore, in vitro analyses demonstrated that DKK3 suppression affected cell adhesion in three DKK3‐expressing lung adenocarcinoma cell lines and that DKK3‐knockdown cells were less invasive in comparison to control cells. These results suggest that DKK3 plays a role in the progression of lung adenocarcinoma by promoting cell adhesion and invasion. DKK3 might be a new extracellular cancer therapeutic target, and it seems important to clarify molecular mechanisms underlying the DKK3 functions depending on cell context.

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“…Some studies have shown that Dickkopf (DKK) 3 promotes cell survival by suppressing superoxideproducing enzyme or by inhibiting inflammation (8,9). DKK3 is classified as a DKK glycoprotein family member that regulates cell fate during embryogenesis.…”

Section: Introductionmentioning

confidence: 99%

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

Yang

Nowrangi

Liang

et al. 2020

Preprint

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Background: Intracerebral hemorrhage (ICH) is the most devastating stroke subtype, with a poor prognosis and few proven treatments. Neuroinﬂammation is associated with ICH-induced brain injury and unfavorable outcomes. There is growing evidence that Dickkopf (DKK) 3 plays a key role in the adaptive anti-inflammatory and neuroprotective responses following intracerebral hemorrhage. This study aimed to evaluate the protective effects of DKK3 against brain edema and neuroinflammation in a mice model of ICH. Methods: Male, adult CD1 mice were subjected to sham or ICH surgery using a collagenase injection model. ICH animals received either recombinant DKK3, Kremen-1 siRNA, or DVL-1 siRNA. The neurobehavioral deficits were evaluated at 24 h, 72 h, and 28 days after ICH induction. Western blot and immunofluorescence were employed to examine the expression and localization of DKK3, Kremen-1, Dishevelled-1 (DVL-1), c-JUN N-terminal kinase (JNK), Activator protein-1 (AP-1), cleaved caspase-1, NF-κB, and IL-1β in the brain. Results: The expression of endogenous DKK3 and DVL-1 was transiently decreased after ICH compared to that in the sham group. Compared to the mice of ICH, exogenous rDKK3 administration reduced the brain water content and affected the neurological functions in ICH mice. Moreover, DKK3 was colocalized with Kremen-1 in microglia. Using a Kremen-1 or DVL-1 siRNA-induced in vivo knockdown approach, we demonstrated that the effects of DKK3 against ICH were mediated , at least partly, by the Kremen-1 and DVL-1 pathways. Conclusions: DKK3 improves the neurological outcomes, potentially by decreasing JNK/AP-1 mediated inflammation, thereby ameliorating the short- and long-term sequelae after ICH.

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Dickkopf 3 attenuates xanthine dehydrogenase expression to prevent oxidative stress‐induced apoptosis

Cited by 11 publications

References 41 publications

Meridianin C inhibits the growth of YD‐10B human tongue cancer cells through macropinocytosis and the down‐regulation of Dickkopf‐related protein‐3

Meridianin C inhibits the growth of YD‐10B human tongue cancer cells through macropinocytosis and the down‐regulation of Dickkopf‐related protein‐3

Dickkopf‐related protein 3 promotes cell adhesion and invasion during progression of lung adenocarcinoma

DKK3 attenuates JNK and AP-1 induced inflammation via Kremen-1 and DVL-1 in mice following intracerebral hemorrhage

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