Breast cancer (BC) is the most common malignancy in women worldwide. Wnt signaling is involved in tumorigenesis and cancer progression, and is closely associated with the characteristics of BC. Variation in the expression of exosomal microRNAs (miRNAs) modulates key cancer phenotypes, such as cellular proliferation, epithelial‑mesenchymal transition, metastatic potential, immune evasion and treatment resistance. The present review aimed to discuss the importance of Wnt signaling and exosomal miRNAs in regulating the occurrence and development of BC. In addition, the present review determined the crosstalk between Wnt signaling and exosomal miRNAs, and highlighted potential diagnostic biomarkers and therapeutic targets.

Wnt signaling is a highly conserved evolutionary pathway that plays a key role in regulation of embryonic development, as well as tissue homeostasis and regeneration. Abnormalities in Wnt signaling are associated with tumorigenesis and development, leading to poor prognosis in patients with cancer. However, the pharmacological effects and mechanisms underlying Wnt signaling and its inhibition in cancer treatment remain unclear. In addition, potential side effects of inhibiting this process are not well understood. Therefore, the present review outlines the role of Wnt signaling in tumorigenesis, development, metastasis, cancer stem cells, radiotherapy resistance and tumor immunity. The present review further identifies inhibitors that target Wnt signaling to provide a potential novel direction for cancer treatment. This may facilitate early application of safe and effective drugs targeting Wnt signaling in clinical settings. An in-depth understanding of the mechanisms underlying inhibition of Wnt signaling may improve the prognosis of patients with cancer.

Compared to an incisional skin or mucosal wound, a tooth extraction wound results in far more soft tissue loss. A blood clot instantly fills the gap left by the extracted tooth. An embryonic type of bone forms during the healing of extraction wounds, and mature bone only later replaces it. Osteocytes in embryonic bone, also known as coarse fibrillar bone or immature bone, differ from those in adult bone in terms of number, size, and irregular arrangement. This immature bone is more radiolucent than mature bone due to the higher cell density and the smaller volume of calcified intercellular material. The Wnt gene family contains genes that encode secreted signaling proteins that have good promise for promoting bone regeneration. However, we still have a limited understanding the interplay of the molecular elements of the Wnt pathway in signal transduction, from ligand detection on the cell surface to transcription of target genes in the nucleus. We discuss the function of Wnt signaling molecules in this review, in tissue repair following tooth extraction and present recent results about these molecules. Conclusions: Wnt signaling activity helps to hasten bone regeneration while bone healing is slowed down by mutations in LRP5/6 or β-catenin.

Endometrial cancer (EC) ranks as the sixth most common malignancy in women around the world. Although low‑grade and early‑stage EC commonly have an excellent prognosis, ~20% of EC patients experience an unfavorable prognosis. Identifying the pathogenesis and novel therapeutic targets may help address this group of patients. Non‑coding (nc)RNAs, such as long non‑coding RNAs (lncRNAs), microRNAs and circular RNAs (circRNAs), have been associated with EC occurrence and development. In addition, the aberrant activation of the Wnt/β‑catenin signaling pathway can promote the proliferation, invasion, migration and epithelial‑to‑mesenchymal transition (EMT) of EC cells. The network of ncRNAs has also been demonstrated to inhibit or activate the Wnt/β‑catenin signaling pathway. In the present review, ncRNAs, the Wnt/β‑catenin signaling pathway, and their crosstalk in EC were summarized and highlighted. This information is expected to provide novel insights into improving the management of EC using RNA as therapeutics.

Triple-Negative Breast Cancer is the most aggressive form and accounts the 15%-25% of all breast cancer. Receptors are absent in triple-negative breast cancer, which makes them unresponsive to the current hormonal therapies. The patients with TNBC are left with the option of cytotoxic chemotherapy. The Wnt pathways are connected to cancer, and when activated, they result in mammary hyperplasia and tumors. The tumor suppressor microRNAs can block tumor cell proliferation, invasion, and migration, lead to cancer cell death, and are also known to down-regulate the WNT signaling. Nanoparticles with microRNA have been seen to be more effective when compared with their single release. In this review, we have tried to understand how Wnt signaling plays a crucial role in TNBC, EMT, metastasis, anti-drug resistance, and regulation of Wnt by microRNA. The role of nano-carriers in delivering micro-RNA. The clinical biomarkers, including the present state-of-the-art, involve novel pathways of Wnt.

Wnt signaling is an evolutionary cell-to-cell coordination mechanism and it is highly critical for a variety of physiological processes of an organism\'s body, including stem cell regeneration, proliferation, division, migration, polarity of a cell, determining fate of the cell and specification of neural crest, neural symmetry and morphogenesis. Wnts are extracellular secreted glycol proteins, consisted of a family of 19 human proteins that represent the complex nature of the regulatory structure and physiological efficiency of signaling. Moreover, a Wnt/β-catenin-dependent pathway and the β-catenin-independent pathway that is further classified into the Planar Cell Polarity and Wnt/Ca2+ pathways have been established as key signaling nodes downstream of the frizzled (Fz/Fzd) receptor, and these nodes are extensively analyzed at biochemical and molecular levels. Genetic and epigenetic activities that ultimately characterize the pathway and its subsequent responses contribute to Wnt-β-catenin signaling pathway hypo or hyper-activation and is associated with the variety of human disorders progression most significantly cancers. Recognizing how this mechanism operates is crucial to the advancement of cancer prevention therapies or regenerative medicine methods.

Tsukushi (TSK), a leucine-rich peptidoglycan in the extracellular compartment, mediates multiple signaling pathways that are critical for development and metabolism. TSK regulates signaling pathways that eventually control cellular communication, proliferation, and cell fate determination. Research on TSK has become more sophisticated in recent years, illustrating its involvement in the physiology and pathophysiology of neural, genetic, and metabolic diseases. In a recent study, we showed that TSK therapy reversed the pathophysiological abnormalities of the hydrocephalic (a neurological disorder) brain in mice. This review summarizes the roles of TSK in key signaling processes in the mammalian development, disorders, and evaluating its possible therapeutic and diagnostic potential.

Here, we present a rarely seen example of bilateral meningiomas exhibiting different malignancy grades, I (meningothelial) and II (atypical), recorded in a 72-year-old patient. The presence of two separated lesions of different grades in a single patient can elucidate meningioma progression. To this end, the involvement of specific protein markers of epithelial to mesenchymal transition (EMT), the process responsible for progression, was tested in both tumors. Protein expression status of specific epithelial (E-cadherin) and mesenchymal markers (N-cadherin, SNAIL&SLUG and TWIST1) was investigated. Furthermore, markers that are connected to Wnt signaling pathway-beta-catenin, GSK3beta and DVL1-were also analyzed. For signs of neurofibromatosis and schwanomatosis genetic testing was performed. Immunohistochemistry evaluated by immunoreactivity score (IRS) was used to determine the signal strengths and proteins\' location. Our results indicated that, in comparison to the grade I tumor, mesenchymal markers SNAIL and SLUG were upregulated in the atypical meningioma. TWIST1, beta-catenin and GSK3beta were upregulated in both grades, while E-cadherin was partially lost. A pronounced cadherin switch could not be established; however, N-cadherin showed widespread tissue presence. Genetic testing did not detect changes of NF2 or SMARCB1 genes denying germline origin of the lesions. The rare presence of two different grades in one patient elucidate previously unknown molecules involved in meningioma progression.

Introduction: Wnt signaling is a signal transduction pathway that plays a vital role in embryonic development and normal tissue preservation. Dysfunction of it gives rise to various diseases like cancer, Alzheimer\'s, metabolic and skeletal disorders, kidney and liver disease, etc. Thus, targeting Wnt pathway can be a potential approach to design and develop novel therapeutic classes.Areas covered: Authors provided an overview of Wnt modulators from 2014 to 2020. Different heterocyclic scaffolds and their pharmacology from a total of 104 PCT applications have been summarized.Expert opinion: The scientific community is working extensively to bring first in the class molecule to the market which targets Wnt pathway. Lorecivivint, Wnt inhibitor, for the treatment of knee Osteoarthritis and SM-04554, Wnt activator, for the treatment of androgenetic alopecia are currently under Phase III. Other molecules, LGK-974, RXC-004, ETC-159, CGX-1321, PRI-724, CWP-232291 and BC-2059 are also under different stages of clinical development for the treatment of cancer. Antibody based Wnt modulator, OTSA101-DTPA-90Y is currently under Phase I for the treatment of Relapsed or Refractory Synovial Sarcoma while OMP-18R5 is under Phase I for Metastatic Breast Cancer.  Ongoing preclinical/clinical trials will define the role of the Wnt pathway in different therapeutic areas and open new opportunities.

The wound healing that follows myocardial infarction is a complex process involving multiple mechanisms, such as inflammation, angiogenesis and fibrosis. In the last two decades, the involvement of WNT signaling has been extensively studied and effects on virtually all aspects of this wound healing have been reported. However, as often is the case in a newly emerging field, inconsistent and sometimes even contradictory findings have been reported. The aim of this systematic review is to provide a comprehensive overview of studies in which the effect of interventions in WNT signaling were investigated in in vivo models of cardiac injury. To this end, we used different search engines to perform a systematic search of the literature using the key words \"WNT and myocardial and infarction\". We categorized the interventions according to their place in the WNT signaling pathway (ligand, receptor, destruction complex or nuclear level). The most consistent improvements of the wound healing response were observed in studies in which the acylation of WNT proteins was inhibited by administering porcupine inhibitors, by inhibiting of the downstream glycogen synthase kinase-3β (GSK3β) and by intervening in the β-catenin-mediated gene transcription. Interestingly, in several of these studies, evidence was presented for activation of cardiomyocyte proliferation around the infarct area. These findings indicate that inhibition of WNT signaling can play a valuable role in the repair of cardiac injury, thereby improving cardiac function and preventing the development of heart failure.