Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil

Menezes, Marina de Pádua Nogueira; Oshima, Celina Tizuko Fujiyama; Badiglian-Filho, Levon; Gomes, Thiago Simão; Barrezueta, Luis Fernando Mesias; Stávale, João Norberto; Gonçalves, Wagner José

doi:10.1590/s1516-31802011000500007

Cited by 9 publications

(7 citation statements)

References 15 publications

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“…In our patient cohort we were not able to confirm this for FZD5 alone, but the combined analysis of WNT5A and FZD5 expression showed that patients with low WNT5A and low FZD5 expression had a longer disease-specific survival than patients with high WNT5A and high FZD5 expression. Besides prostate cancer FZD5 is downregulated in endometrial adenocarcinoma [ 44 ]. In addition, motility and invasion of melanoma cells is increased through WNT5A/FZD5 signaling [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Role of WNT5A receptors FZD5 and RYK in prostate cancer cells

et al. 2018

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Prostate cancer is the most common malignancy in men and has a high propensity to metastasize to bone. WNT5A has recently been implicated in the progression of prostate cancer, however, the receptors that mediate its effects remain unknown. Here, we identified Wnt receptors that are highly expressed in prostate cancer and investigated which of these receptors mediate the anti-tumor effects of WNT5A in prostate cancer in vitro.Extensive in vitro analyses revealed that the WNT5A receptors FZD5 and RYK mediate the anti-tumor effects of WNT5A on prostate cancer cells. Knock-down of FZD5 completely abrogated the anti-proliferative effect of WNT5A in PC3 cells. In contrast, knock-down of RYK and FZD8 did not rescue the inhibition of proliferation after WNT5A overexpression. In contrast, RYK knock-down inhibited the pro-apoptotic effect of WNT5A in PC3 cells by 60%, whereas the knock-down of either FZD5 or FZD8 further stimulated apoptosis after WNT5A overexpression (by 33% and 234%, respectively). Surface plasmon resonance analysis indicated that WNT5A has a 30% stronger binding response to FZD5 than to RYK. Further investigations using a tissue microarray revealed that expression of RYK is increased in advanced prostate cancer tumor stages, but is not associated with survival of prostate cancer patients. In contrast, patients with low local FZD5 expression, in particular in combination with low WNT5A expression, showed a longer disease-specific survival.In conclusion, WNT5A/FZD5 and WNT5A/RYK signaling are both involved in mediating the pro-apoptotic and anti-proliferative effects of WNT5A in prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Role of WNT5A receptors FZD5 and RYK in prostate cancer cells

et al. 2018

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“…Deregulation of the Wnt/β-catenin signaling pathway by inactivating β-catenin mutations was found in approximately 10%–45% of EmCa [77]. In contrast, no significant difference in Wnt1, FZD1 and Wnt5 expression between EmCa and normal endometrium was found [78]. Additionally, Wnt and Hedgehog expressions were lower in EmCa compared to normal endometrium, which may suggest that Notch acts a tumor suppressor in these pathways [70, 79].…”

Section: Notch Crosstalk To Many Signaling Pathways In Endometrial Camentioning

confidence: 99%

Molecular cues on obesity signals, tumor markers and endometrial cancer

Daley-Brown¹,

Oprea‐Ilies²,

Lee³

et al. 2015

Hormone Molecular Biology and Clinical Investigation

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Tumor markers are important tools for early diagnosis, prognosis, therapy response and endometrial cancer monitoring. A large number of molecular and pathologic markers have been described in types I and II endometrial cancers, which has served to define the main oncogenic, epidemiological, genetic, clinical and histopathological features. Ongoing attempts to stratify biological markers of endometrial cancer are presented. However, data on changes in tumor marker profiles in obesity-related endometrial cancer are scarce. Obesity is a pandemic in Western countries that has an important impact on endometrial cancers, albeit through not very well-defined mechanisms. Although endometrial cancer is more common in Caucasian women, higher mortality is found in African Americans who also show higher incidence of obesity. Here, we describe how obesity signals (estrogen, leptin, leptin induced-molecules, Notch; cytokines and growth factors) could affect endometrial cancer. Leptin signaling and its crosstalk may be associated to the more aggressive and poor prognosis type II endometrial cancer, which affects more postmenopausal and African-American women. In this regard, studies on expression of novel molecular markers (Notch, interleukin-1 and leptin crosstalk outcome) may provide essential clues for detection, prevention, treatment and prognosis.

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“…Another study analyzed a link between Wnt10a and Wnt10b expression and clinical characteristics of EC; while Wnt10a was shown to be specific only for histological type of EC, expression of Wnt10b correlated with EC histology, grade, FIGO stage and lymphatic spread 38 . However, other authors did not find significant differences in the immunoexpressions of Wnt1 and Wnt5a in EC and atrophic endometrium 45 . This evidence suggests that various types of Wnt proteins may play different roles in tumor progression.…”

Section: Discussionmentioning

confidence: 76%

The Role of Wnt/Beta-Catenin Pathway, SATB1 and SATB2 in Endometrial Cancer Patients

Sadłecki¹,

Bodnar²,

Marszałek³

et al. 2021

Preprint

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Wnt/β-catenin signaling pathway plays an established role in various diseases and is considered a hallmark of endometrial cancer (EC). Special AT-rich sequence-binding protein 1 and 2 (SATB1 and SATB2) are nuclear matrix-associated proteins involved in chromatin remodeling and regulation of gene expression. SATB1 promotes the progression of numerous types of cancers, whereas SATB2 acts as a tumor suppressor. Despite a recent progress in our knowledge about EC, the exact mechanisms that control their proliferation and metastatic potential still remain unknown. The aim of our study was to investigate the association between Wnt3A, β-catenin, SATB1 and SATB2 protein level and the clinicopathological features of EC patients. 92 EC patients, aged 37-84, were enrolled to our study. The immunoexpression of WNT3A was found in specimens from all EC patients, β-catenin was expressed in 97% of the cases, SATB1 in 87%. The significant association between Wnt3a expression and tumor grade was found; moreover mean IRS for Wnt3a turned out to be significantly lower in high-grade tumors than in low-grade malignancies (p=0.038). In turn, immunoexpression of β-catenin varied significantly across FIGO stages and was associated with the presence of lymph node metastases. Mean IRS for β-catenin in patients with lymph node metastases was significantly lower than in those without (p = 0.028). The Kaplan-Meier analyses demonstrated a stepwise impairment of cancer overall survival with increasing SATB1 expression. In conclusion, both Wnt/β-catenin signaling pathway and SATB1 contribute to progression of EC. Downregulation of β-catenin may predispose to lymphatic spread of EC. In turn, downregulation of Wnt3a seems to be characteristic for high-grade tumors, but probably does not play a role in formation of lymph node metastases. The important role of SATB1 as a predictor of poor survival and could be helpful in establishing a more accurate prognosis in endometrial cancer patients.

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Canonical and noncanonical Wnt pathways: a comparison between endometrial cancer type I and atrophic endometrium in Brazil

Cited by 9 publications

References 15 publications

Role of WNT5A receptors FZD5 and RYK in prostate cancer cells

Role of WNT5A receptors FZD5 and RYK in prostate cancer cells

Molecular cues on obesity signals, tumor markers and endometrial cancer

The Role of Wnt/Beta-Catenin Pathway, SATB1 and SATB2 in Endometrial Cancer Patients

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