HOXD13 suppresses prostate cancer metastasis and BMP4-induced epithelial-mesenchymal transition by inhibiting SMAD1.
Int J Cancer
; 148(12): 3060-3070, 2021 06 15.
Article
en En
| MEDLINE
| ID: mdl-33521930
ABSTRACT
The HOX genes are a group of highly conserved Homeobox-containing genes that control the body plan organization during development. However, their contributions to tumorigenesis and tumor progression remain uncertain and controversial. Here we provided evidence of tumor-suppressive activity of HOXD13 in prostate cancer. HOXD13 depletion contributes to more aggressiveness of prostate cancer cells in vitro and in vivo. These effects were corroborated in a metastatic mice model, where we observed more bone metastatic lesions formed by prostate cancer cells with HOXD13 ablation. Mechanistically, HOXD13 prevents BMP4-induced epithelial-mesenchymal transition (EMT) by inhibiting mothers against decapentaplegic homolog 1 (SMAD1) transcription. Both bioinformation and our tissue microarray cohort data show that HOXD13 expression inversely correlated in advanced prostate cancer patient specimens. Our findings establish HOXD13 as a negative regulator of prostate cancer progression and metastasis by preventing BMP4/SMAD1 signaling, and potentially suggest new strategies for targeting metastatic prostate cancer.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Neoplasias de la Próstata
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Factores de Transcripción
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Neoplasias Óseas
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Proteínas de Homeodominio
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Proteína Smad1
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Proteína Morfogenética Ósea 4
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int J Cancer
Año:
2021
Tipo del documento:
Article
País de afiliación:
China