Zuo Tao, Shan Jinshuai, Liu Yang, Xie Rong, Yu Xiaochun, Wu Chen
College of Life Sciences, Hebei University, Baoding 071002, Hebei, P.R. China.
Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd, Duarte, California, 91010, USA.
Transl Oncol. 2018 Apr;11(2):346-352. doi: 10.1016/j.tranon.2018.01.021. Epub 2018 Feb 8.
N-Acetylgalactosaminyltransferase-14 (GALNT14) is a member of acetylgalactosaminyltransferases family. We have shown that GALNT14 could promote breast cancer cell invasion. However, the underlying molecular mechanism is unclear. Here, using yeast two hybrid, we find that EGF-containing fibulin-like extracellular matrix protein 2 (EFEMP2) interacts with GALNT14. Both in vitro and in vivo binding assays show that EFEMP2 is associated with GALNT14. Moreover, we find that GALNT14 mediates glycosylation of EFEMP2. EFEMP2 significantly increased the invasion ability of breast cancer cells including MCF-7 and MBA-MD-231 cells, and this phenomenon is suppressed by knockdown expression of GALNT14. In addition, the GALNT14-dependent O-glycosylation of EFEMP-2 regulates the stability of EFEMP-2 protein in breast cancer cells. Taken together, our results demonstrate a novel molecular mechanism underlying breast cancer invasion.
N-乙酰半乳糖胺基转移酶-14（GALNT14）是乙酰半乳糖胺基转移酶家族的一员。我们已经表明，GALNT14可以促进乳腺癌细胞的侵袭。然而，其潜在的分子机制尚不清楚。在这里，我们使用酵母双杂交技术发现，含表皮生长因子的纤连蛋白样细胞外基质蛋白2（EFEMP2）与GALNT14相互作用。体外和体内结合试验均表明EFEMP2与GALNT14相关。此外，我们发现GALNT14介导EFEMP2的糖基化。EFEMP2显著增强了包括MCF-7和MBA-MD-231细胞在内的乳腺癌细胞的侵袭能力，而这种现象在GALNT14的敲低表达后受到抑制。此外，GALNT14依赖的EFEMP-2的O-糖基化调节乳腺癌细胞中EFEMP-2蛋白的稳定性。综上所述，我们的结果揭示了一种乳腺癌侵袭的新分子机制。
