Cheng Teng, Wei Rui, Jiang Guiying, Zhou Ying, Lv Mengqin, Dai Yun, Yuan Yuan, Luo Danfeng, Ma Ding, Li Fei, Xi Ling
Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Tumour Biol. 2017 Jul;39(7):1010428317717122. doi: 10.1177/1010428317717122.
XPNPEP2 is a proline hydrolytic enzyme that hydrolyzes several biologically active peptides and causes a loss of substrate activity. However, its function in cancer is still unknown. Our study showed that XPNPEP2 expression was significantly upregulated in cervical cancer tissues compared with normal cervical tissues and cervical intraepithelial neoplasm tissues. Statistical analysis showed that XPNPEP2 expression was associated with the International Federation of Gynecology and Obstetrics stage and lymph node metastasis. Overexpression of XPNPEP2 in SiHa and HeLa cells promoted cell invasion and migration without affecting cell proliferation and apoptosis. Mechanistically, we found that XPNPEP2 facilitated cervical cancer cell invasion and migration by inducing epithelial-mesenchymal transition. Furthermore, we demonstrated that XPNPEP2 had significant effects on the metastasis of xenografted tumors in vivo. Collectively, our findings identify the novel function of XPNPEP2 in the metastasis of cervical cancer and suggest that XPNPEP2 could be a novel potential therapeutic target for the treatment of cervical cancer.
XPNPEP2是一种脯氨酸水解酶，可水解多种生物活性肽并导致底物活性丧失。然而，其在癌症中的功能仍不清楚。我们的研究表明，与正常宫颈组织和宫颈上皮内瘤变组织相比，XPNPEP2在宫颈癌组织中的表达显著上调。统计分析表明，XPNPEP2表达与国际妇产科联盟分期和淋巴结转移相关。XPNPEP2在SiHa和HeLa细胞中的过表达促进了细胞侵袭和迁移，而不影响细胞增殖和凋亡。机制上，我们发现XPNPEP2通过诱导上皮-间质转化促进宫颈癌细胞侵袭和迁移。此外，我们证明XPNPEP2对体内异种移植肿瘤的转移有显著影响。总体而言，我们的研究结果确定了XPNPEP2在宫颈癌转移中的新功能，并表明XPNPEP2可能是治疗宫颈癌的新的潜在治疗靶点。
