RESUMO
BACKGROUND AND AIMS: Aberrant expression of B7 homolog 3 protein (B7-H3) has been detected in various cancers including colorectal cancer (CRC) and implicated in modulating multiple biological functions of CRC cells. However, its role in CRC metastasis has not yet been determined. This study aims to explore and unravel the underlying mechanisms through which B7-H3 contributes to migration, invasion and actin cytoskeleton in CRC. METHODS: The expression of B7-H3 and LIMK1 in CRC tumor samples was determined by IHC staining. Transwell and F-actin immunofluorescence staining assays were performed to explore the role of B7-H3 in migration, invasion and actin filament accumulating of CRC cells. RNA-seq and Western blot assays were used to investigate the molecular mechanisms. RESULTS: B7-H3 was highly expressed in CRC tissues and positively associated with poor prognosis of CRC patients by immunohistochemistry. Migration and invasion assays showed that B7-H3 knockdown significantly inhibited the migration and invasion of CRC cells. B7-H3 overexpression had the opposite effect. Moreover, we determined that B7-H3 could regulate actin cytoskeleton and the RhoA/ROCK1/LIMK1 pathway by F-actin immunofluorescence staining and Western blot. Importantly, the BDP5290, an inhibitor of the RhoA/ROCK1/(LIM domain kinase 1) LIMK1 axis, reversed the effects of B7-H3 overexpression on actin filament accumulating, migration, and invasion of CRC cells. CONCLUSIONS: Our study concluded that B7-H3 facilitated CRC cell actin filament accumulating, migration, and invasion through the RhoA/ROCK1/LIMK1 axis.
Assuntos
Citoesqueleto de Actina , Movimento Celular , Neoplasias Colorretais , Quinases Lim , Invasividade Neoplásica , Transdução de Sinais , Quinases Associadas a rho , Proteína rhoA de Ligação ao GTP , Feminino , Humanos , Masculino , Citoesqueleto de Actina/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Quinases Lim/metabolismo , Quinases Lim/genética , Quinases Associadas a rho/metabolismo , Quinases Associadas a rho/genética , Proteína rhoA de Ligação ao GTP/metabolismo , Antígenos B7/genética , Antígenos B7/metabolismoRESUMO
Pancreatic cancer is one of the common malignant tumors of the digestive system and is known as the "king of cancers". It is extremely difficult to diagnose at an early stage, the disease progresses rapidly, and the effect of chemotherapy and radiotherapy is poor, so the prognosis of pancreatic cancer patients is very poor. Numerous studies have suggested that hypoxia is closely related to the development and progression of pancreatic cancer. Inadequate blood supply and desmoplasia in the microenvironment of pancreatic cancer can result in its extreme hypoxia. This hypoxic microenvironment can further contribute to angiogenesis and desmoplasia. Hypoxia is mediated by the complex hypoxia inducible factor (HIF) signaling pathway and plays an important role in the formation of a highly immunosuppressive microenvironment and the metastasis of pancreatic cancer. Further work on the hypoxic microenvironment will help clarify the specific mechanisms of the role of hypoxia in pancreatic cancer and provide a basis for the realization of hypoxia-targeted therapeutic and diagnostic strategies.