Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, China.
Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130033, China.
Biomed Pharmacother. 2017 May;89:1370-1377. doi: 10.1016/j.biopha.2017.03.017. Epub 2017 Mar 18.
The molecular mechanisms underlying the growth and metastasis of colorectal cancer (CRC) remain largely unknown. Sulfatase-2 (SULF2) was found to play critical roles in human cancers. Recent study reported that SULF1/2 overexpression resulted in increased viability and proliferation, and augmented cell migration in CRC cells. However, the expression of SULF2 and its underlying molecular mechanisms in CRC remain unknown. In this study, we found that the expressions of SULF2 in CRC tissues and cell lines were significantly increased compared to control groups. Increased expression of SULF2 was associated with malignant clinical features and poor prognosis of CRC patients. Loss of SULF2 significantly prohibited the proliferation, cell cycle progression, migration and invasion of HT29 cells, while restoration of SULF2 significantly promoted these cellular functions of SW480 cells. In vivo tumorigenicity and liver metastasis assays confirmed that SULF2 knockdown significantly reduced the growth and metastatic abilities of HT29 cells in nude mice. Furthermore, SULF2 knockdown reduced the levels of p-Akt and p-Erk1/2 in HT29 cells, while SULF2 overexpression showed opposite effects on the expressions of these proteins in SW480 cells. In all, SULF2 promotes the growth and metastasis of CRC probably by activating Akt and Erk1/2 pathways. SULF2 potentially serves as a promising biomarker and therapeutic target in CRC.
结直肠癌（CRC）生长和转移的分子机制在很大程度上尚不清楚。磺基转移酶-2（SULF2）被发现在人类癌症中发挥关键作用。最近的研究报道，SULF1/2 的过表达导致 CRC 细胞活力和增殖增加，并增强细胞迁移。然而，CRC 中 SULF2 的表达及其潜在的分子机制尚不清楚。在这项研究中，我们发现 SULF2 在 CRC 组织和细胞系中的表达明显高于对照组。SULF2 的表达增加与 CRC 患者的恶性临床特征和不良预后相关。SULF2 的缺失显著抑制了 HT29 细胞的增殖、细胞周期进程、迁移和侵袭，而 SULF2 的恢复则显著促进了 SW480 细胞的这些细胞功能。体内肿瘤发生和肝转移实验证实，SULF2 敲低显著降低了 HT29 细胞在裸鼠中的生长和转移能力。此外，SULF2 敲低降低了 HT29 细胞中 p-Akt 和 p-Erk1/2 的水平，而 SULF2 过表达对 SW480 细胞中这些蛋白的表达则表现出相反的影响。总之，SULF2 通过激活 Akt 和 Erk1/2 通路促进 CRC 的生长和转移。SULF2 可能是 CRC 有前途的生物标志物和治疗靶点。
