Li Xiang, Zhang Guohui, Wang Yan, Elgehama Ahmed, Sun Yang, Li Lele, Gu Yanhong, Guo Wenjie, Xu Qiang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China.
Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Biomed Pharmacother. 2017 Mar;87:366-374. doi: 10.1016/j.biopha.2016.12.103. Epub 2017 Jan 6.
Periplakin (PPL), a member of the plakin protein family, has been reported to be down-expressed in urothelial carcinoma. The role of PPL in human colorectal cancer, however, remains largely unknown. Also little is known about the contribution of PPL to the malignant property of colorectal cancer and the intracellular function of PPL. In this study, we demonstrated that PPL was apparently down-expressed in colon carcinomas compared with normal and para-carcinoma tissues, which was correlated with the tumor size. Enforced expression of PPL in HT29 cells inhibited its proliferation evidenced by decreased expression of phosphorylated ERK and PCNA. Furthermore, PPL overexpression could reduce metastasis and epithelial-mesenchymal transition (EMT) of HT29 cells, with decreased expression of N-cadherin, Snail, Slug and α-SMA while increased expression of E-cadherin. On the contrary, the PPL knockdown could promote the cell proliferation, migratory, invasive and EMT ability of HT29 cells. Moreover, enforced expression of PPL induced G1/G0 cell cycle arrest, with decreased cyclin D1, p-Rb and increased expression of p27, which could be reversed by PPL knockdown. In addition, PPL overexpression inhibited the growth of colon cancer allograft in vivo. Taken together, acted as a tumor suppressor in colon cancer progression, PPL could be a new biomarker or potential therapeutic target in colon cancer.
外周斑蛋白（PPL）是斑蛋白家族的成员之一，据报道其在尿路上皮癌中表达下调。然而，PPL在人类结直肠癌中的作用在很大程度上仍不清楚。关于PPL对结直肠癌恶性特性的贡献以及PPL的细胞内功能也知之甚少。在本研究中，我们证明与正常组织和癌旁组织相比，PPL在结肠癌中明显下调，且这与肿瘤大小相关。在HT29细胞中强制表达PPL可抑制其增殖，表现为磷酸化ERK和PCNA的表达降低。此外，PPL过表达可减少HT29细胞的转移和上皮-间质转化（EMT），N-钙黏蛋白、Snail、Slug和α-平滑肌肌动蛋白的表达降低，而E-钙黏蛋白的表达增加。相反，敲低PPL可促进HT29细胞的增殖、迁移、侵袭和EMT能力。此外，强制表达PPL诱导G1/G0期细胞周期阻滞，细胞周期蛋白D1、磷酸化视网膜母细胞瘤蛋白表达降低，p27表达增加，而敲低PPL可逆转这种情况。此外，PPL过表达在体内抑制结肠癌异种移植物的生长。综上所述，作为结肠癌进展中的肿瘤抑制因子，PPL可能是结肠癌的一种新的生物标志物或潜在的治疗靶点。
