WNT Signaling: an Emerging Mediator of Cancer Cell Metabolism?

Sherwood, Victoria

doi:10.1128/mcb.00992-14

Cited by 128 publications

(112 citation statements)

References 85 publications

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“…Wnt signaling promotes tumor growth, 51,52 and aberrant Wnt signaling has been reported to increase myeloma cell proliferation. 53 Soluble Wnt antagonists inhibit endogenous Wnt signaling and therefore the antisclerostin antibody might promote tumor proliferation by stopping Wnt suppression in the local bone microenvironment.…”

Section: Additive Effects Of Anti-sclerostin Antibody and Zamentioning

confidence: 99%

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma

McDonald

Reagan

Youlten

et al. 2017

Blood

163

161

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Multiple myeloma (MM) is a plasma cell cancer that develops in the skeleton causing profound bone destruction and fractures. The bone disease is mediated by increased osteoclastic bone resorption and suppressed bone formation. Bisphosphonates used for treatment inhibit bone resorption and prevent bone loss but fail to influence bone formation and do not replace lost bone, so patients continue to fracture. Stimulating bone formation to increase bone mass and fracture resistance is a priority; however, targeting tumor-derived modulators of bone formation has had limited success. Sclerostin is an osteocyte-specific Wnt antagonist that inhibits bone formation. We hypothesized that inhibiting sclerostin would prevent development of bone disease and increase resistance to fracture in MM. Sclerostin was expressed in osteocytes from bones from naive and myeloma-bearing mice. In contrast, sclerostin was not expressed by plasma cells from 630 patients with myeloma or 54 myeloma cell lines. Mice injected with 5TGM1-eGFP, 5T2MM, or MM1.S myeloma cells demonstrated significant bone loss, which was associated with a decrease in fracture resistance in the vertebrae. Treatment with anti-sclerostin antibody increased osteoblast numbers and bone formation rate but did not inhibit bone resorption or reduce tumor burden. Treatment with anti-sclerostin antibody prevented myeloma-induced bone loss, reduced osteolytic bone lesions, and increased fracture resistance. Treatment with anti-sclerostin antibody and zoledronic acid combined increased bone mass and fracture resistance when compared with treatment with zoledronic acid alone. This study defines a therapeutic strategy superior to the current standard of care that will reduce fractures for patients with MM

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Section: Additive Effects Of Anti-sclerostin Antibody and Zamentioning

confidence: 99%

Inhibiting the osteocyte-specific protein sclerostin increases bone mass and fracture resistance in multiple myeloma

McDonald

Reagan

Youlten

et al. 2017

Blood

163

161

View full text Add to dashboard Cite

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“…Upon activation of the Wnt signalling pathway, these proteasomes are inhibited, and β-catenin is able to translocate to the nucleus. Abnormal dephosphorylation of β-catenin, such as that observed in cancer development, can also result in increased nuclear translocation (8).…”

mentioning

confidence: 99%

Regulation of β-Catenin Phosphorylation by PR55β in Adenoid Cystic Carcinoma

Ishibashi

Ishii

Sugiyama

et al. 2018

CGP

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Abstract. Background Adenoid cystic carcinoma (AdCC) is a rare cancer that arises within the secretory glands, mainly the salivary gland. For head and neck AdCC, the age-adjusted incidence rate is 4.5 cases per 100,000 individuals and exhibits a slight female predominance (1). The risks for delayed recurrence and metastasis in other organs are higher in AdCC than in other oral cancers, such as squamous cell carcinoma (SCC), because of the propensity of AdCC to invade neighbouring tissues and migrate into blood vessels (2, 3). Despite the fact that hundreds of malignant AdCC tumors have been characterized at the molecular level, the underlying regulatory mechanisms of this cancer type remain unclear.To date, many clinical AdCC studies have reported that poor prognosis is associated with pathological features such as AdCC type and grade (4). Histological specimens can be divided into three groups: tubular, cribriform, or solid. Because patients with solid AdCC are especially likely to present with distant metastases, they are the strongest candidates for further surveillance and preventative treatment (5). The use of molecular approaches to elucidate the pathways involved in invasion and migration should significantly add to our understanding of AdCC pathogenesis. Using cell sublines derived from ACCS (an AdCC cell line) by in vivo selection in mice, Ishii et al. (6) demonstrated that interactions between β-catenin and E-cadherin are associated with cell adhesion and lead to tumor metastasis. Further analysis of the molecular mechanisms involved in AdCC should contribute to the identification of potential therapeutic targets.β-catenin is a key molecule in Wnt signalling and plays an important role in cell growth, development, and cancer. The phosphorylation of β-catenin is regulated by several kinases and phosphatases (7). In the absence of extracellular activation, phosphorylated β-catenin is degraded by proteasomes in the cytoplasm. Upon activation of the Wnt signalling pathway, these proteasomes are inhibited, and 53 This article is freely accessible online.

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“…Wnt/␤-catenin signaling promotes dorsal cell fates in frogs and fish, and it is also hyperactivated in several types of cancer (54,55); however, its regulation remains incompletely understood. Here, we report that LZAP, a tumor suppressor, regulates Wnt/␤-catenin signaling via the suppression of inhibitory phosphorylation of GSK3 in fish embryos and in cancer (Fig.…”

Section: Discussionmentioning

confidence: 99%