HIF-1α interacts with Kindlin-2 and influences breast cancer elasticity: A study based on shear wave elastography imaging.
Cancer Med
; 9(14): 4971-4979, 2020 07.
Article
em En
| MEDLINE
| ID: mdl-32436609
ABSTRACT
Breast cancer was the most frequent and the second most deadly cancer in women in 2018 in China; thus, early diagnosis of breast cancer is important. Studies have reported that tissue stiffness promotes cancer progression through increased collagen or fibrosis. Shear wave elastography (SWE) is a technique for measuring tissue stiffness. However, the mechanisms underlying cancer tissue stiffness or fibrosis are not entirely clear. Hypoxia-inducible factor 1 (HIF-1α) is expressed in response to hypoxia and contributes to tumor progression and metastasis. Kindlin-2 is an important co-activator of integrin. We have reported that Kindlin-2 influences breast cancer stiffness and metastasis. In this study, SWE was used to determine the maximum elasticity (Emax ) of patients before operation or core needle biopsy. The specimens were used for staining. Knockdown, overexpression, co-immunoprecipitation, and immunofluorescence assays were used to explore the relationship between HIF-1α and Kindlin-2. We found that HIF-1α and Kindlin-2 were highly expressed in invasive breast cancer and that the expression levels of HIF-1α and Kindlin-2 were correlated with Emax . HIF-1α interacts with Kindlin-2. Besides, HIF-1α and Kindlin-2 influence the expression of P4HA1, an important protein in collagen biogenesis through the integrin/FAK pathway. Our study first identified a new mechanism of invasive breast cancer stiffness by linking HIF-1α and Kindlin-2 to collagen biogenesis. Therefore, based on SWE, Emax could be a physical biomarker of invasive breast cancer for early, noninvasive diagnosis, and HIF-1α and Kindlin-2 could be pathological markers for early diagnosis and targeted therapy.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
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Subunidade alfa do Fator 1 Induzível por Hipóxia
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Técnicas de Imagem por Elasticidade
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Proteínas de Membrana
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Proteínas de Neoplasias
Limite:
Adult
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Female
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Humans
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Middle aged
Idioma:
En
Revista:
Cancer Med
Ano de publicação:
2020
Tipo de documento:
Article