RESUMEN
Remodeling of basement membrane proteins contributes to tumor progression towards the metastatic stage. One of these proteins, laminin 521 (LN521), sustains embryonic and induced pluripotent stem cell self-renewal, but its putative role in cancer is poorly described. In the present study we found that LN521 promotes colorectal cancer (CRC) cell self-renewal and invasion. siRNA-mediated knockdown of endogenously-produced laminin alpha 5, as well as treatment with neutralizing antibodies against integrin α3ß1 and α6ß1, were able to reverse the effect of LN521 on self-renewal. Exposure of CRC cells to LN521 enhanced STAT3 phosphorylation, and incubation with STAT3 inhibitors Napabucasin and Stattic was sufficient to block the LN521-driven self-renewal increase. Robust expression of laminin alpha 5 was detected in 7/10 liver metastases tissue sections collected from CRC patients as well as in mouse liver metastasis xenografts, in most cases within areas expressing metastasis cancer stem cell markers such as c-KIT and CD44v6. Finally, retrospective analysis of multiple CRC datasets highlighted the significant association between high LN521 mRNA expression and poor clinical outcome in colorectal cancer patients. Collectively our results indicate that high Laminin 521 expression is a frequent feature of metastatic dissemination in CRC and that it promotes cell invasion and self-renewal, the latter through engagement of integrin isoforms and activation of STAT3 signaling.
Asunto(s)
Biomarcadores de Tumor/metabolismo , Autorrenovación de las Células , Neoplasias Colorrectales/patología , Laminina/metabolismo , Neoplasias Hepáticas/secundario , Células Madre Neoplásicas/patología , Factor de Transcripción STAT3/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Laminina/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Ratones , Invasividad Neoplásica , Células Madre Neoplásicas/metabolismo , Pronóstico , Estudios Retrospectivos , Factor de Transcripción STAT3/genética , Transducción de Señal , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
Fusobacterium nucleatum (F. nucleatum) is a Gram-negative obligate anaerobe bacterium in the oral cavity and plays a role in several oral diseases, including periodontitis and gingivitis. Recently, several studies have reported that the level of F. nucleatum is significantly elevated in human colorectal adenomas and carcinomas compared to that in adjacent normal tissue. Several researchers have also demonstrated that F. nucleatum is obviously associated with colorectal cancer and promotes the development of colorectal neoplasms. In this review, we have summarized the recent reports on F. nucleatum and its role in colorectal cancer and have highlighted the methods of detecting F. nucleatum in colorectal cancer, the underlying mechanisms of pathogenesis, immunity status, and colorectal cancer prevention strategies that target F. nucleatum.
RESUMEN
Objective To compare the effect between early parenteral nutrition (PN)and enteral nutrition (EN) in postoperative patients with carcinoma of colon and rectum.Methods We selected 60 cases of colon and rectal carcinoma and randomly divided into PN and EN groups,measured some index including weight,diameter of the upper arm,HGB,LYM,ALB,PAB and term of exhausting.Results Weight,diameter of the upper ann,LYM,ALB in EN could catch an relative approximation to the usual; the other index in EN were also better than PN.Conclusion EN is the better way for early nutritional support after surgery of colon and rectal carcinoma.