The performance of the proposed methodology is investigated by applying a state-feedback controller to two GRN models: a melanomaWNT5A Boolean network and a p53-MDM2 negative feedback loop Boolean network, when the cost of the undesirable states, and thus the identity of the undesirable genes, is learned using the proposed methodology.
Taken together, these results indicate that Wnt5a activates the NF-κB pathway and has an immunomodulatory effect on melanoma through the secretion of cytokines and chemokines.
Wnt5a has been implicated in melanoma progression and metastasis, although the exact downstream signaling events that contribute to melanoma metastasis are poorly understood.
Overexpression of wingless-type MMTV integration site family 5A (WNT5A) plays a significant role in melanoma cancer progression; however, the mechanism(s) involved remains unknown.
Furthermore, silencing of GLUT1 in the melanoma cells resulted in the increased expression of WNT5A and the decreased ability of invasion and proliferation in the melanoma cells.
To understand how store-operated calcium entry (SOCE) contributes to Wnt5A-induced malignancy in melanoma models, we examined the expression and function of STIM1 and Orai1 in patient-derived malignant melanoma cells, previously characterized as either highly invasive (metastatic) or noninvasive.
Furthermore, increased WNT5A expression in BRAFi-resistant melanomas correlates with a specific transcriptional signature, which identifies potential therapeutic targets to reduce clinical BRAFi resistance.
As ROR2 has been shown to specifically interact with the non-canonical Wnt ligand, Wnt5A, this corroborates our earlier data implicating Wnt5A as a mediator of melanoma metastasis.
Phenylmethimazole decreases Toll-like receptor 3 and noncanonical Wnt5a expression in pancreatic cancer and melanoma together with tumor cell growth and migration.
Cytoplasmic WNT5A showed a trend of increasing expression with melanoma progression (P = 0.013), whereas there was diminishing p16(ink4a) expression (P = 0.006).
The intervention procedure is applied to a WNT5A network to reduce the risk of metastasis in melanoma, and the identification procedure is applied to a Drosophila melanogaster segmentation polarity gene network to identify regulatory function perturbation.
Expression of Wnt5a, MMP7, and beta-catenin was determined in 40 primary uveal melanomas by immunohistochemistry and correlated with patient prognosis.
Furthermore, inhibition of PKC before Wnt5A treatment blocked Snail expression, implying that Wnt5A can potentiate melanoma metastasis via the induction of EMT in a PKC-dependent manner.
Hierarchical clustering analysis of the expression data was able to distinguish between the melanoma and nonmelanoma samples and further stratified the melanoma samples into two groups differentiated by high expression of the genes involved in beta-catenin activation (EGFR and WNT5A) and the MAPK/ERK pathway (BRAF, FOS, and JUN).