RESUMEN
Colorectal cancer (CRC) is the second leading cause of cancer-related mortality worldwide. Although CRC patients' survival is improved with surgical resection and immunotherapy, metastasis and recurrence remain major problems leading to poor prognosis. Therefore, exploring pathogenesis and identifying specific biomarkers are crucial for CRC early diagnosis and targeted therapy. CCDC113, a member of CCDC families, has been reported to play roles in ciliary assembly, ciliary activity, PSCI, asthma and early lung cancer diagnosis. However, the functions of CCDC113 in CRC still remain unclear. In this study, we find that CCDC113 is significantly highly expressed in CRC. High expression of CCDC113 is significantly correlated with CRC patients' poor prognosis. CCDC113 is required for CRC tumorigenesis and metastasis. RNA-seq and TCGA database analysis indicate that CCDC113 is positively correlated with TGF-ß signaling pathway. TGF-ß signaling pathway inhibitor galunisertib could reverse the increased proliferation and migration ability of CRC cells caused by CCDC113 overexpression in vitro and in vivo. These results indicate that CCDC113 promotes CRC tumorigenesis and metastasis via TGF-ß signaling pathway. In conclusion, it is the first time to explore the functions and mechanisms of CCDC113 in CRC tumorigenesis and metastasis. And CCDC113 may be a potential biomarker and therapeutic target for CRC intervention.
Asunto(s)
Carcinogénesis , Proliferación Celular , Neoplasias Colorrectales , Transducción de Señal , Factor de Crecimiento Transformador beta , Animales , Femenino , Humanos , Masculino , Ratones , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Pronóstico , Pirazoles/farmacología , Quinolinas/farmacología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
An achiral counteranion-induced reversal of enantioselectivity in Ni(II)-catalyzed Friedel-Crafts alkylation/annulation of 2-naphthols with ß,γ-unsaturated α-keto esters was achieved. Using imidazolidine pyrroloimidazolone pyridine as the ligand and Ni(acac)2 as the Lewis acid, diverse naphthopyran derivatives were obtained in good yields (up to 94% yield) and high enantioselectivities (up to 99% ee). In the presence of Ni(OTf)2 as the Lewis acid, a series of chiral naphthopyran derivatives were obtained in good yields and with a controlled switch in stereoselectivity. DFT calculations reveal that the achiral counteranions regulate H-bonding interactions between counteranions with the N-H of the ligand and the O-H of 2-naphthol.