TRIM7 suppresses cell invasion and migration through inhibiting HIF-1α accumulation in clear cell renal cell carcinoma.
Cell Biol Int
; 46(4): 554-567, 2022 Apr.
Article
em En
| MEDLINE
| ID: mdl-34936717
ABSTRACT
Clear cell renal cell carcinoma (ccRCC) is one frequent form of urologic malignancy characterized by deregulated hypoxia-inducible factor signaling, genetic and epigenetic alterations. Metastasis is the leading cause of mortality from ccRCC, and understanding the underlying mechanism of this event will provide better strategies for its management. Here, we identify tripartite motif containing 7 (TRIM7) as a tumor suppressor in ccRCC cells, which negatively regulates hypoxia-inducible factor 1α (HIF-1α) signaling through targeting the proto-oncogene Src. We observed the downregulated expression of TRIM7 in clinical ccRCC tissues and its correlation with the poor prognosis. In Caki-1 cells, depletion of TRIM7 increased cell migration and invasion under normoxic and hypoxic conditions. TRIM7 markedly reduced the abundance of Src protein via the ubiquitin-proteasome pathway. Further study showed that TRIM7 affected HIF-1α accumulation through targeting either the Src-triggered PI3K/AKT/mTOR signaling pathway or reactive oxygen species production. Overall, our findings highlight a novel mechanism for negative regulation of HIF-1 signaling pathway by TRIM7 and define a promising therapeutic strategy for ccRCC by modulating TRIM7.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Ubiquitina-Proteína Ligases
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Proteínas com Motivo Tripartido
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Neoplasias Renais
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article