Background Sirtuin 1 （SIRT1） has been reported to have diverse roles in various biological processes through deacetylation of histone and nonhistone proteins.However,the correlations among SIRT1 protein expression,clinicopathological parameters,and survival of colorectal cancer patients remain unclear.Methods SIRT1 protein expression was measured by immunohistochemistry in a paraffin-embedded tissue microarray,including 120 paired colorectal cancer and normal mucosa tissues.The correlations among SIRT1 protein expression,clinicopathological features,and prognosis were analyzed.Results All samples （100%） were positive for SIRT1,with variable staining in the cytoplasm rather than in the nucleus.There was significant difference in SIRT1 overexpression between adenocarcinomas and normal mucosal tissue （P〈0.01,x2 test）.SIRT1 overexpression was more frequently observed in advanced-stage tumors （P=0.046,0.002,x2test）.SIRT1 overexpression was significantly correlated with poor overall survival （P=0.013,log-rank test） and diseasefree survival （P=0.012,log-rank test）.Conclusions SIRT1 overexpression correlated with advanced stage and poor prognosis.SIRT1 may play an important role in the progression of colorectal cancer.
Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.
