Wnt signaling pathway

The Wnt signaling pathways are signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. 

The Wnt signaling pathway is a group of signal transduction pathways made of proteins that pass signals into a cell through cell surface receptors. 

Wnt signaling pathways use either nearby cell-cell communication (paracrine) or same-cell communication (autocrine). 

Wnt signaling controls both development and homeostasis, and its disruption is implicated in a wide range of human diseases.

The name of the pathway Wnt,  is a combination of “Wingless” and “Int-1.” 

This pathway plays key roles in various processes like cell proliferation, cell fate determination, and embryonic development. 

There are 19 WNT ligands which have partially overlapping expression and functions.

Three Wnt signaling pathways have been characterized.

Canonical Wnt pathway, 

Noncanonical planar cell polarity pathway, 

 Noncanonical Wnt/calcium pathway. 

All three pathways are activated by the binding of a Wnt-protein ligand to a Frizzled family receptor, which passes the biological signal to the Dishevelled protein inside the cell. 

The canonical Wnt pathway leads to regulation of gene transcription.

The noncanonical planar cell polarity pathway regulates the cytoskeleton that is responsible for the shape of the cell. 

The noncanonical Wnt/calcium pathway regulates calcium inside the cell.

Wnt signaling controls include cell fate specification, cell proliferation and cell migration, necessary for proper formation of important tissues including bone, heart and muscle.

Wnt signaling acts as ligands to activate the different Wnt pathways via paracrine and autocrine routes.

The Wnt/calcium pathway role is to help regulate calcium release from the endoplasmic reticulum (ER) in order to control intracellular calcium levels. 

Wnt signaling plays a critical role in embryonic development. 

Wnt signaling is also involved in the axis formation of specific body parts and organ systems later in development. 

Sonic hedgehog (Shh) and Wnt morphogenetic signaling gradients establish the dorsoventral axis of the central nervous system during neural tube axial patterning. 

Wnt proteins guide the axons of the spinal cord in an anterior-posterior direction.

Wnt signaling induces blood formation from stem cells.

Wnt3 leads to mesoderm committed cells with hematopoietic potential.

Wnt1 antagonizes neural differentiation.

Wnt1 is a major factor in self-renewal of neural stem cells, allowing for regeneration of nervous system cells, and promotes neural stem cell proliferation.

Wnt signaling aspects include: germ cell determination, gut tissue specification, hair follicle development, lung tissue development, trunk neural crest cell differentiation, nephron development, ovary development and sex determination.

Wnt signaling antagonizes or inhibits heart formation, during development.

Small molecule Wnt inhibitors are used to produce cardiomyocytes from pluripotent stem cells.

Proliferation and growth of embryonic stem cells are mediated through Wnt signaling, which increases nuclear and cytoplasmic β-catenin. 

Increased β-catenin can initiate transcriptional activation of proteins such as cyclin D1 and c-myc, which control the G1 to S phase transition in the cell cycle. 

Entry into the S phase causes DNA replication and ultimately mitosis, which are responsible for cell proliferation.

This proliferation increase is directly paired with cell differentiation because as the stem cells proliferate, they also differentiate,

allowing for overall growth and development of specific tissue systems during embryonic development. 

In the circulatory system Wnt3a leads to proliferation and expansion of hematopoietic stem cells needed for red blood cell formation.

Wnt-addicted cells hijack and depend on constant stimulation of the Wnt pathway to promote their uncontrolled growth, survival and migration In cancer.

Wnt signaling can become independent of regular stimuli, through mutations in downstream oncogenes and tumor suppressor genes that become permanently activated.

Wnt signaling  mediates  ell migration during embryonic development allows for the establishment of body axes, tissue formation, limb induction and several other processes.

Wnt signaling also induces cell migration through the control of the migration behavior of neuroblasts, neural crest cells, myocytes, and tracheal cells.

Wnt signaling is involved in epithelial-mesenchymal transition (EMT), a process allowing epithelial cells to transform into mesenchymal cells so that they are no longer held in place at the laminin. 

Wnt leads to upregulation of glucose transporters in the cell membrane in order to increase glucose uptake from the bloodstream. 

Wnt protein that increases this sensitivity in skeletal muscle cells.

Wnt signaling has had an association with cancer. 

Canonical Wnt pathway activity is involved in the development of benign and malignant breast tumors, and has a role in tumor chemoresistance.

Wnt pathway activity is revealed by elevated levels of β-catenin in the nucleus and/or cytoplasm, which can be detected with immunohistochemical staining and Western blotting. 

The Increased β-catenin expression is correlated with poor prognosis in breast cancer patients. 

Breast tumors can metastasize due to Wnt involvement in epithelial to mesenchymal transition.

Repression of Wnt/β-catenin signaling can prevent EMT, which can inhibit metastasis.

Wnt signaling has been implicated in the development of  cancers. 

Changes in CTNNB1 expression, which is the gene that encodes β-catenin, can be measured in breast, colorectal, melanoma, prostate, lung, and other cancers. 

Increased expression of Wnt ligand-proteins are observed in the development of glioblastoma, oesophageal cancer and ovarian cancer respectively.

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