ULK1 negatively regulates Wnt signaling by phosphorylating Dishevelled

Hwang, Sun-Hong; Bang, Sunhoe; Kang, Keonwook; Kang, Deborah; Chung, Jongkyeong

doi:10.1016/j.bbrc.2018.11.139

Cited by 12 publications

(5 citation statements)

References 25 publications

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“…Thus, the non-inhibition of GSK-3β activity by DVL leads to β-catenin phosphorylation, ubiquitination and then a diminution in WNT/β-catenin pathway activity. DVL is phosphorylated by active ULK1 to become inactive [ 253 ]. Thus, following autophagy induction, DVL is inhibited and the WNT/β-catenin pathway is attenuated [ 254 , 255 ].…”

Section: Interplay Between Glycolysis and Autophagy In The Cancer Processmentioning

confidence: 99%

The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions

Vallée

Lecarpentier²,

Vallée

2021

Cancers

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The canonical WNT/β-catenin pathway is upregulated in cancers and plays a major role in proliferation, invasion, apoptosis and angiogenesis. Nuclear β-catenin accumulation is associated with cancer. Hypoxic mechanisms lead to the activation of the hypoxia-inducible factor (HIF)-1α, promoting glycolytic and energetic metabolism and angiogenesis. However, HIF-1α is degraded by the HIF prolyl hydroxylase under normoxia, conditions under which the WNT/β-catenin pathway can activate HIF-1α. This review is therefore focused on the interaction between the upregulated WNT/β-catenin pathway and the metabolic processes underlying cancer mechanisms under normoxic conditions. The WNT pathway stimulates the PI3K/Akt pathway, the STAT3 pathway and the transduction of WNT/β-catenin target genes (such as c-Myc) to activate HIF-1α activity in a hypoxia-independent manner. In cancers, stimulation of the WNT/β-catenin pathway induces many glycolytic enzymes, which in turn induce metabolic reprogramming, known as the Warburg effect or aerobic glycolysis, leading to lactate overproduction. The activation of the Wnt/β-catenin pathway induces gene transactivation via WNT target genes, c-Myc and cyclin D1, or via HIF-1α. This in turn encodes aerobic glycolysis enzymes, including glucose transporter, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase kinase 1 and lactate dehydrogenase-A, leading to lactate production. The increase in lactate production is associated with modifications to the tumor microenvironment and tumor growth under normoxic conditions. Moreover, increased lactate production is associated with overexpression of VEGF, a key inducer of angiogenesis. Thus, under normoxic conditions, overstimulation of the WNT/β-catenin pathway leads to modifications of the tumor microenvironment and activation of the Warburg effect, autophagy and glutaminolysis, which in turn participate in tumor growth.

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Section: Interplay Between Glycolysis and Autophagy In The Cancer Processmentioning

confidence: 99%

The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions

Vallée

Lecarpentier²,

Vallée

2021

Cancers

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“…Of note, Disheveled (Dsh) plays a central role in the Wnt/ β -catenin pathway, which is a key pathway that determines the differentiation fate of cells during development 172 . Interestingly, ULK1 can phosphorylate Dsh at multiple sites, such as Ser239, Ser247, and Ser254 in PDZ-DEP, as well as Ser239, Ser247, Ser254, Ser266, Ser376, and Ser554 173 . Moreover, ULK1 is of great importance in cancer-related signaling pathways.…”

Section: The Molecular Basis Underlying the Regulation Mechanism Of Ulk1mentioning

confidence: 99%

“…AMPK-activated ULK1 can help embryonic stem cells maintain self-renewal and maintain versatility 106 . ULK1 can phosphorylate multiple sites of DSH in Wnt signaling pathway, which may affect Wnt signaling 173 . Besides, ULK1 phosphorylates Ser843 in the binding region of mineralocorticoid receptor ligand in renal intercalated cells, to maintain water salt balance 282 .…”

Section: Autophagic and Non-autophagic Functions Of Ulk1 In Human Dis...mentioning

confidence: 99%

Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications

Zou

Liao

Zhen

et al. 2022

Acta Pharmaceutica Sinica B

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“…β‐catenin is also facilitate adaptation to microenvironmental conditions such as hypoxia and oxidative stress and this explains the regulatory feedback mechanism via negatively regulation of autophagy 98 . In the starvation condition, autophagy showed adverse regime for Wnt signals with ULK1 stimulating degradation by dishevelled phosphorylate (dvl) 99 . This degradation mediated by its ubiquitylation, which promotes p62 association and subsequently its p62‐mediated binding of LC3.…”

Section: Role Of Autophagy In Cscs Differentiationmentioning

confidence: 99%

Differential mechanisms of autophagy in cancer stem cells: Emphasizing gastrointestinal cancers

El‐Gowily

Abosheasha

2020

Cell Biochemistry & Function

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Gastrointestinal (GI) cancers are one of the most common forms of malignancies and still are the most important cause of cancer‐related mortality worldwide. Autophagy is a conserved catabolic pathway involving lysosomal degradation and recycling of whole cellular components, which is essential for cellular homeostasis. For instance, it acts as a pivotal intracellular quality control and repair mechanism but also implicated in cell reformation during cell differentiation and development. Indeed, GI cancer stem cells (CSCs) are thought to be responsible for tumour initiation, traditional therapies resistance, metastasis and tumour recurrence. Molecular mechanisms of autophagy in normal vs CSCs gain great interest worldwide. Here, we shed light on the role of autophagy in normal stem cells differentiation for embryonic progression and its role in maintaining the activity and self‐renewal capacity of CSCs which offer novel viewpoints on promising cancer therapeutic strategies based on the differential roles of autophagy in CSCs.

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ULK1 negatively regulates Wnt signaling by phosphorylating Dishevelled

Cited by 12 publications

References 25 publications

The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions

The Key Role of the WNT/β-Catenin Pathway in Metabolic Reprogramming in Cancers under Normoxic Conditions

Autophagy and beyond: Unraveling the complexity of UNC-51-like kinase 1 (ULK1) from biological functions to therapeutic implications

Differential mechanisms of autophagy in cancer stem cells: Emphasizing gastrointestinal cancers

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