EFEMP2 Mediates GALNT14-Dependent Breast Cancer Cell Invasion.

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成员。我们已经表明GALNT14能够促进乳腺癌细胞的侵袭。然而，潜在的分子机制尚不清楚。在此，通过酵母双杂交实验，我们发现含表皮生长因子的类纤维连接蛋白细胞外基质蛋白2（EFEMP2）与GALNT14相互作用。体外和体内结合实验均表明EFEMP2与GALNT14相关联。此外，我们发现GALNT14介导EFEMP2的糖基化。EFEMP2显著提高了包括MCF - 7和MBA - MD - 231细胞在内的乳腺癌细胞的侵袭能力，并且这种现象可通过敲低GALNT14的表达而被抑制。此外，EFEMP - 2的GALNT14依赖性O - 糖基化调节乳腺癌细胞中EFEMP - 2蛋白的稳定性。综上所述，我们的研究结果揭示了乳腺癌侵袭潜在的一种新的分子机制。