Vitamin D receptor activation is a feasible therapeutic target to impair adrenocortical tumorigenesis

Bueno, Ana Carolina; Marrero-Gutiérrez, Junier; Silva, Danillo C. de Almeida e; Leal, Letícia Ferro; Montaldi, Ana Paula; Ramalho, Fernando Silva; Vêncio, Ricardo Z. N.; Castro, Margaret de; Antonini, Sonir Roberto Rauber

doi:10.1016/j.mce.2022.111757

Cited by 4 publications

(7 citation statements)

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“…Rap1 and Ras signals have been shown to cooperatively initiate and sustain ERK signal transduction in various tumors, promoting tumor invasion and migration, including PCa [ 28 , 29 ]. Interestingly, a study in adrenal cortical cancer highlighted that VDR can activate Rap1 signaling, resulting in antitumor proliferation effects [ 30 ]. Therefore, these signaling pathways may constitute crucial mechanisms through which the VD metabolic pathway regulates the biological behavior of tumors.…”

Section: Discussionmentioning

confidence: 99%

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer

Ding,

Wang,

Tang

et al. 2024

Nutr Metab (Lond)

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Background Previous studies have unequivocally demonstrated that the vitamin D (VD) metabolism pathway significantly influences prognosis and sensitivity to hormone therapy in prostate cancer (PCa). However, the precise underlying mechanism remains unclear. Methods We performed molecular profiling of 1045 PCa patients, leveraging genes linked to VD synthesis and VD receptors. We then identified highly variable gene modules with substantial associations with patient stratification. Subsequently, we intersected these modules with differentially expressed genes between PCa and adjacent paracancerous tissues. Following a meticulous process involving single-factor regression and LASSO regression to eliminate extraneous variables and construct a prognostic model. Within the high-risk subgroup defined by the calculated risk score, we analyzed their differences in cell infiltration, immune status, mutation landscape, and drug sensitivity. Finally, we selected Apolipoprotein E (APOE), which featured prominently in this model for further experimental exploration to evaluate its potential as a therapeutic target. Results The prognostic model established in this study had commendable predictive efficacy. We observed diminished infiltration of various T-cell subtypes and reduced expression of co-stimulatory signals from antigen-presenting cells. Mutation analysis revealed that the high-risk cohort harbored a higher frequency of mutations in the TP53 and FOXA genes. Notably, drug sensitivity analysis suggested the heightened responsiveness of high-risk patients to molecular inhibitors targeting the Bcl-2 and MAPK pathways. Finally, our investigation also confirmed that APOE upregulates the proliferative and invasive capacity of PCa cells and concurrently enhances resistance to androgen receptor antagonist therapy. Conclusion This comprehensive study elucidated the potential mechanisms through which this metabolic pathway orchestrates the biological behavior of PCa and findings hold promise in advancing the development of combination therapies in PCa.

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Section: Discussionmentioning

confidence: 99%

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer

Ding,

Wang,

Tang

et al. 2024

Nutr Metab (Lond)

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“…Vitamin D receptor is overexpressed in H295R cells due to hypermethylation. By inhibiting Wnt/β-catenin signaling through the activation of VDR, calcitriol inhibits tumor proliferation and growth ( 137 ). The combination role of mitotane and calcitriol, regulates the VDR and Wnt/β-catenin signaling, exerting antiproliferative effects ( 139 ).…”

Section: Drugs and Inhibitorsmentioning

confidence: 99%

Wnt/β-catenin signaling pathway in the tumor progression of adrenocortical carcinoma

Tai,

Shang

2024

Front. Endocrinol.

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Adrenocortical carcinoma (ACC) is an uncommon, aggressive endocrine malignancy with a high rate of recurrence, a poor prognosis, and a propensity for metastasis. Currently, only mitotane has received certification from both the US Food and Drug Administration (FDA) and the European Medicines Agency for the therapy of advanced ACC. However, treatment in the advanced periods of the disorders is ineffective and has serious adverse consequences. Completely surgical excision is the only cure but has failed to effectively improve the survival of advanced patients. The aberrantly activated Wnt/β-catenin pathway is one of the catalysts for adrenocortical carcinogenesis. Research has concentrated on identifying methods that can prevent the stimulation of the Wnt/β-catenin pathway and are safe and advantageous for patients in view of the absence of effective treatments and the frequent alteration of the Wnt/β-catenin pathway in ACC. Comprehending the complex connection between the development of ACC and Wnt/β-catenin signaling is essential for accurate pharmacological targets. In this review, we summarize the potential targets between adrenocortical carcinoma and the Wnt/β-catenin signaling pathway. We analyze the relevant targets of drugs or inhibitors that act on the Wnt pathway. Finally, we provide new insights into how drugs or inhibitors may improve the treatment of ACC.

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“…Quanto às aplicações terapêuticas do calcitriol destaca-se o ensaio realizado por Bueno et al 31 . Estes autores realizaram estudos in vitro e in vivo quanto à participação do calcitriol e respectivo análogo sintético seocalcitol no desenvolvimento de carcinomas adrenocorticais (CAC).…”

Section: Ações Em Doenças Autoimunes Tumorais Infectocontagiosasunclassified

“…Estes tumores ocorrem com maior frequência em crianças na primeira e em adultos na quarta década de vida. Nos Estados Unidos da América (EUA), a incidência anual estimada aproxima-se de 0,2 a 0,3 casos por milhão (Bernstein e Gurney, citados em 31 ). Apresenta-se, contudo, particularmente elevada no sudeste e sul do Brasil, cerca de 10 a 15 vezes superior à observada nos EUA.…”

Section: Ações Em Doenças Autoimunes Tumorais Infectocontagiosasunclassified

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Vitamina D - Aspectos Fisiológicos, Nutricionais, Imunológicos, Genéticos. Ações em doenças autoimunes, tumorais, infecciosas. Funções musculoesqueléticas e cognitivas

Ruscalleda

2023

Rev. Med. (São Paulo)

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Vitamina D representa de fato, um hormônio esteroide lipossolúvel com funções endócrinas, parácrinas e autócrinas. Este artigo buscou realizar revisão de aspectos fisiológicos, ambientais, nutricionais e genéticos relacionados a esta vitamina, classificação dos níveis séricos da forma circulante representativa do status, bem locais de armazenamento em tecidos. Sugestões são apresentadas, de acordo com literatura consultada, quanto a hábitos alimentares, exposição solar adequada, suplementação oral e/ou necessidade de doses de manutenção, riscos de toxicidade. Funções imunológicas, imunomoduladoras, participação a nível celular e tecidual em doenças autoimunes, tumorais, infecto-contagiosas, com ênfase ao SARS-CoV-2 também foram abordadas. Entre as inúmeras ações da vitamina D, houve destaque à participação no metabolismo musculoesquelético, ocorrência de quedas, particularmente entre os idosos, sistema nervoso central, com ênfase à cognição, demência, doença de Alzheimer. Aspectos consensuais ou controversos também foram abordados, bem como sugestões de novos estudos a nível mundial para esclarecimento de resultados questionáveis.

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Vitamin D receptor activation is a feasible therapeutic target to impair adrenocortical tumorigenesis

Cited by 4 publications

References 70 publications

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer

Exploration of vitamin D metabolic activity-related biological effects and corresponding therapeutic targets in prostate cancer

Wnt/β-catenin signaling pathway in the tumor progression of adrenocortical carcinoma

Vitamina D - Aspectos Fisiológicos, Nutricionais, Imunológicos, Genéticos. Ações em doenças autoimunes, tumorais, infecciosas. Funções musculoesqueléticas e cognitivas

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