Wnt Pathway: An Integral Hub for Developmental and Oncogenic Signaling Networks

Sharma, Monica; Pruitt, Kevin

doi:10.3390/ijms21218018

Cited by 40 publications

(37 citation statements)

References 184 publications

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“…Wnt signalling pathways regulate complex normal biological processes such as cell differentiation, development, tissue homeostasis, and wound healing. However, when the Wnt pathway is aberrantly regulated, it can be associated with bone anomalies, neurodevelopmental disorders, cancer, and cardiovascular diseases, among other diseases [ 19 ]. Wnt signalling is a particularly complex pathway that leads to the activation of two main, alternative branches: the canonical and the noncanonical pathway.…”

Section: Resultsmentioning

confidence: 99%

“…Activation of the noncanonical pathway does not depend on β-catenin-driven transcription. Instead, it relies on changes that affect cytoskeletal organization and calcium homeostasis [ 19 ]. PORCN (protein-serine O-palmitoleoyltransferase porcupine) mediates palmitoylation of Wnt proteins, which is an essential modification necessary for their correct secretion and binding to the Frizzled receptors, thus, being a major regulator of Wnt signalling [ 20 , 21 , 22 ].…”

Section: Resultsmentioning

confidence: 99%

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De Novo PORCN and ZIC2 Mutations in a Highly Consanguineous Family

Castilla‐Vallmanya

Gürsoy

Giray-Bozkaya

et al. 2021

IJMS

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We present a Turkish family with two cousins (OC15 and OC15b) affected with syndromic developmental delay, microcephaly, and trigonocephaly but with some phenotypic traits distinct between them. OC15 showed asymmetrical skeletal defects and syndactyly, while OC15b presented with a more severe microcephaly and semilobal holoprosencephaly. All four progenitors were related and OC15 parents were consanguineous. Whole Exome Sequencing (WES) analysis was performed on patient OC15 as a singleton and on the OC15b trio. Selected variants were validated by Sanger sequencing. We did not identify any shared variant that could be associated with the disease. Instead, each patient presented a de novo heterozygous variant in a different gene. OC15 carried a nonsense mutation (p.Arg95*) in PORCN, which is a gene responsible for Goltz-Gorlin syndrome, while OC15b carried an indel mutation in ZIC2 leading to the substitution of three residues by a proline (p.His404_Ser406delinsPro). Autosomal dominant mutations in ZIC2 have been associated with holoprosencephaly 5. Both variants are absent in the general population and are predicted to be pathogenic. These two de novo heterozygous variants identified in the two patients seem to explain the major phenotypic alterations of each particular case, instead of a homozygous variant that would be expected by the underlying consanguinity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

De Novo PORCN and ZIC2 Mutations in a Highly Consanguineous Family

Castilla‐Vallmanya

Gürsoy

Giray-Bozkaya

et al. 2021

IJMS

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“…In the presence of canonical Wnt ligands, the scaffold protein Disheveled (DVL) is activated, which induces the dissociation of the β-catenin–ubiquitin E3 ligase degradation complex and non-phosphorylated β-catenin. β-catenin accumulates in the cytoplasm and translocates to the nucleus [ 2 , 12 , 20 ]. Nuclear β-catenin binds to and activates T cell factor (TCF) and lymphoid enhancer-binding (LEF) TFs, which directly bind to specific DNA sequences, enhancing the transcription of genes such as Cyclin D, c-Myc, and Axin2 and inhibiting transcription of other genes such as E-cadherin and the tumor suppressor p53 [ 19 , 25 ].…”

Section: Wnt Pathway Overviewmentioning

confidence: 99%

“…Wingless-related integration site (Wnt) signaling is a complex cell communication system that controls aspects of organ development, stem cell proliferation, injury and repair responses, and homeostatic maintenance of tissues [ 10 , 11 ]. Hyperactive or hypoactive Wnt signaling may result in embryonic abnormalities and/or adult organ dysfunction and diseases, in particular cancers [ 12 ]. There are multiple ligands (activating and inhibiting) and receptors and intracellular kinase-controlled complexes in the Wnt pathway that lead to either activation or inhibition of gene transcription.…”

Section: Introductionmentioning

confidence: 99%

CrossTORC and WNTegration in Disease: Focus on Lymphangioleiomyomatosis

Evans

Obraztsova

Lin

et al. 2021

IJMS

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The mechanistic target of rapamycin (mTOR) and wingless-related integration site (Wnt) signal transduction networks are evolutionarily conserved mammalian growth and cellular development networks. Most cells express many of the proteins in both pathways, and this review will briefly describe only the key proteins and their intra- and extracellular crosstalk. These complex interactions will be discussed in relation to cancer development, drug resistance, and stem cell exhaustion. This review will also highlight the tumor-suppressive tuberous sclerosis complex (TSC) mutated, mTOR-hyperactive lung disease of women, lymphangioleiomyomatosis (LAM). We will summarize recent advances in the targeting of these pathways by monotherapy or combination therapy, as well as future potential treatments.

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“…The pathway of the Wnt (Wingless and Integrated-1) family is one of the fundamental mechanisms that directs cellular proliferation and cell fate during embryonic development and tissue homeostasis. Consequently, mutations in this pathway are often linked to human birth defects, or different diseases, including cancer [ 15 ]. As discussed by Choi, the Wnt/β-catenin pathway also plays a role during the formation of new hair growth or hair loss [ 16 ].…”

mentioning

confidence: 99%