Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies

Daams, Renée; Massoumi, Ramin

doi:10.3390/ijms21239203

Cited by 13 publications

(15 citation statements)

References 51 publications

(53 reference statements)

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“…Many of those genes are linked to functions and processes that drive cancer. For instance, serine/threonine protein kinase NLK was demonstrated to localize in the nucleus of breast cancer cells and protect the cells from apoptosis [ 50 ]. The tumorigenic function of the SREBF1 transcription factor, which was found to be overexpressed and positively associated with metastasis and poor prognosis in breast cancer patients, has been linked to oncogenic activation of the PI3K/AKT/mTOR signaling pathway [ 51 ].…”

Section: Resultsmentioning

confidence: 99%

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

et al. 2021

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Epigenetic aberrations are linked to sporadic breast cancer. Interestingly, certain dietary polyphenols with anti-cancer effects, such as pterostilbene (PTS), have been shown to regulate gene expression by altering epigenetic patterns. Our group has proposed the involvement of DNA methylation and DNA methyltransferase 3B (DNMT3B) as vital players in PTS-mediated suppression of candidate oncogenes and suggested a role of enhancers as target regions. In the present study, we assess a genome-wide impact of PTS on epigenetic marks at enhancers in highly invasive MCF10CA1a breast cancer cells. Following chromatin immunoprecipitation (ChIP)-sequencing in MCF10CA1a cells treated with 7 μM PTS for 9 days, we discovered that PTS leads to increased binding of DNMT3B at enhancers of 77 genes, and 17 of those genes display an overlapping decrease in the occupancy of trimethylation at lysine 36 of histone 3 (H3K36me3), a mark of active enhancers. We selected two genes, PITPNC1 and LINC00910, and found that their enhancers are hypermethylated in response to PTS. These changes coincided with the downregulation of gene expression. Of importance, we showed that 6 out of 17 target enhancers, including PITPNC1 and LINC00910, are bound by an oncogenic transcription factor OCT1 in MCF10CA1a cells. Indeed, the six enhancers corresponded to genes with established or putative cancer-driving functions. PTS led to a decrease in OCT1 binding at those enhancers, and OCT1 depletion resulted in PITPNC1 and LINC00910 downregulation, further demonstrating a role for OCT1 in transcriptional regulation. Our findings provide novel evidence for the epigenetic regulation of enhancer regions by dietary polyphenols in breast cancer cells.

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Section: Resultsmentioning

confidence: 99%

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

et al. 2021

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“…NLK null mice die late in pregnancy or just after birth due to compromised lung development. Depending on the mouse strain, the hematopoietic system ranges from unaffected to severely compromised [74]. The bone marrow niche is also disrupted with reduced fat tissue and stromal cells.…”

Section: Kinases and Anemiamentioning

confidence: 99%

“…The bone marrow niche is also disrupted with reduced fat tissue and stromal cells. NLK regulates the Wnt pathway but can also influence STAT3 and interferon signaling [74].…”

Section: Kinases and Anemiamentioning

confidence: 99%

Signaling Pathways That Regulate Normal and Aberrant Red Blood Cell Development

Wilkes

Shibuya

Sakamoto

2021

Genes

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Blood cell development is regulated through intrinsic gene regulation and local factors including the microenvironment and cytokines. The differentiation of hematopoietic stem and progenitor cells (HSPCs) into mature erythrocytes is dependent on these cytokines binding to and stimulating their cognate receptors and the signaling cascades they initiate. Many of these pathways include kinases that can diversify signals by phosphorylating multiple substrates and amplify signals by phosphorylating multiple copies of each substrate. Indeed, synthesis of many of these cytokines is regulated by a number of signaling pathways including phosphoinositide 3-kinase (PI3K)-, extracellular signal related kinases (ERK)-, and p38 kinase-dependent pathways. Therefore, kinases act both upstream and downstream of the erythropoiesis-regulating cytokines. While many of the cytokines are well characterized, the nuanced members of the network of kinases responsible for appropriate induction of, and response to, these cytokines remains poorly defined. Here, we will examine the kinase signaling cascades required for erythropoiesis and emphasize the importance, complexity, enormous amount remaining to be characterized, and therapeutic potential that will accompany our comprehensive understanding of the erythroid kinome in both healthy and diseased states.

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“…In this study, we genetically linked Wnd to the Hippo pathway for the first time and provided in vivo evidence that Wnd promotes cell proliferation in some contexts. Nmo (NLK) is involved in diverse developmental and cellular processes and was recently identified as a positive regulator of Yki/YAP activity (Moon et al, 2017;Daams and Massoumi, 2020). Despite its sequence characteristics as a MAPK, no MAPKK has been reported to phosphorylate NLK, and in contrast it can autophosphorylate itself.…”

Section: Nmo Is Essential For Impaired Cell Polarity or Rho1-induced Hippo Inactivationmentioning

confidence: 99%

Wallenda-Nmo Axis Regulates Growth via Hippo Signaling

Liu

2021

Front. Cell Dev. Biol.

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Both Hippo signaling pathways and cell polarity regulation are critical for cell proliferation and the maintenance of tissue homeostasis, despite the well-established connections between cell polarity disruption and Hippo inactivation, the molecular mechanism by which aberrant cell polarity induces Hippo-mediated overgrowth remains underexplored. Here we use Drosophila wing discs as a model and identify the Wnd-Nmo axis as an important molecular link that bridges loss-of-cell polarity-triggered Hippo inactivation and overgrowth. We show that Wallenda (Wnd), a MAPKKK (mitogen-activated protein kinase kinase kinase) family member, is a novel regulator of Hippo pathways in Drosophila and that overexpression of Wnd promotes growth via Nemo (Nmo)- mediated Hippo pathway inactivation. We further demonstrate that both Wnd and Nmo are required for loss-of-cell polarity-induced overgrowth and Hippo inactivation. In summary, our findings provide a novel insight on how cell polarity loss contributes to overgrowth and uncover the Wnd-Nmo axis as an essential additional branch that regulates Hippo pathways in Drosophila.

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Nemo-Like Kinase in Development and Diseases: Insights from Mouse Studies

Cited by 13 publications

References 51 publications

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

Pterostilbene Changes Epigenetic Marks at Enhancer Regions of Oncogenes in Breast Cancer Cells

Signaling Pathways That Regulate Normal and Aberrant Red Blood Cell Development

Wallenda-Nmo Axis Regulates Growth via Hippo Signaling

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