PRR11在结直肠癌中的表达及其对结直肠癌侵袭和转移的影响

Proline-rich protein 11 is highly expressed in colorectal cancer to promote cancer cell invasion and metastasis

目的检测富含脯氨酸蛋白11(proline-rich protein 11,PRR11)在结直肠癌中的表达,探讨其对结直肠癌侵袭和转移的影响。方法应用免疫组织化学检测2015年1月至2018年3月重庆市江津区中心医院136例结直肠癌组织与68例癌旁组织中PRR11的表达;Western blot、RT-PCR及免疫荧光检测PRR11及EMT相关信号分子在结直肠癌细胞中的表达;细胞划痕实验、Transwell小室法检测细胞的迁移、侵袭能力。结果结直肠癌组织中PRR11阳性表达率高于癌旁组织(60.29%vs 1.47%,P<0.01),且与结直肠癌的远处转移、瘤体大小、TNM分期有关(P<0.05);相比于正常结直肠上皮细胞,PRR11在结直肠癌细胞中高表达(P<0.05);过表达PRR11后,癌细胞HT29的迁移和侵袭能力增强,同时伴随明显的β-catenin核转位,且显著增强β-catenin和Vimentin的表达,抑制E-cadherin的表达(P<0.05);相反,沉默PRR11后,HT29的迁移和侵袭能力减弱,且显著抑制β-catenin和Vimentin的表达,增强E-cadherin的表达(P<0.05)。结论 PRR11在结直肠癌中高表达,且可能通过激活Wnt/β-catenin信号通路,促进β-catenin核转位,从而促进结直肠癌的侵袭和转移。

Objective To investigate the expression of proline-rich protein 11(PRR11) in colorectal cancer and its role in regulating the invasion and metastasis of colorectal cancer. Methods The expression of PRR11 was detected using immunohistochemical SP method in 136 specimens of colorectal cancer tissues and 68 adjacent tissues collected from Jiangjin District Central Hospital between January, 2015 and March, 2018. We also examined the expression of PRR11 and epithelial-mesenchymal transition(EMT)-related signal molecules in 3 colorectal cancer cell lines(SW480, HT29 and HCT116) and normal human rectal epithelial cells(HCoEpiC) using Western blotting, RT-PCR and immunofluorescence assay;cell scratch assay and Transwell assay were used to compare the migration and invasion abilities of the colorectal cancer cells. Results The positive expression rate of PRR11 was significantly higher in colorectal cancer tissue than in the adjacent tissues(60.29% vs 1.47%, P<0.01). PRR11 expression was significantly correlated with tumor differentiation, distant metastasis, tumor size and tumor staging(P<0.05). Compared with normal colorectal epithelial cells, the colorectal cancer cell lines expressed high levels of PRR11. Overexpression of PRR11 in HT29 cells significantly enhanced the cell migration and invasion ability, caused obvious β-catenin nuclear translocation, significantly up-regulated the expression of β-catenin and vimentin, and decreased the expression of E-cadherin(P<0.05). Silencing PRR11 significantly lowered the migration and invasion ability of HT29 cells, decreased the expression of β-catenin and vimentin, and increased the expression of E-cadherin(P<0.05). Conclusion PRR11 is highly expressed in colorectal cancer to promote tumor invasion and metastasis possibly by promoting the nuclear translocation of β-catenin via activating the Wnt/β-catenin signaling pathway.