Nasopharyngeal carcinoma (NPC) originates in the nasopharyngeal epithelium and has the highest metastatic rate among head and neck cancers. Distant metastasis is the main reason for treatment failure with the underlying mechanisms remaining unclear. By comparing the expression profiling of NPCs versus non-cancerous nasopharyngeal tissues, we found LACTB was highly expressed in the tumor tissues. We found that elevated expression of the LACTB protein in primary NPCs correlated with poorer patient survival. LACTB is known to be a serine protease and a ubiquitous mitochondrial protein localized in the intermembrane space. Its role in tumor biology remains controversial. We found that the different methylation pattern of LACTB promoter led to its differential expression in NPC cells. Overexpressing LACTB in NPC cells promoted their motility in vitro and metastasis in vivo. While knocking down LACTB reduced the metastasis capability of NPC cells. However, LACTB did not influence cellular proliferation. We further found the role of LACTB in promoting NPC metastasis depended on the activation of ERBB3/EGFR-ERK signaling, which in turn, affected the stability and the following acetylation of histone H3. These findings may shed light on unveiling the mechanisms of NPC metastasis.

鼻咽癌（NPC）起源于鼻咽上皮，在头颈癌中转移率最高。远处转移是治疗失败的主要原因，其潜在机制仍不清楚。通过比较NPCs与非癌性鼻咽组织的表达谱，我们发现LACTB在肿瘤组织中高表达。我们发现在原发性鼻咽癌中LACTB蛋白的表达升高与患者生存期较差有关。已知LACTB是丝氨酸蛋白酶和位于膜间空间的普遍存在的线粒体蛋白。它在肿瘤生物学中的作用仍存在争议。我们发现LACTB的不同甲基化模式启动子导致其在NPC细胞中的差异表达。过度表达LACTB在鼻咽癌细胞促进其体外运动和体内转移。同时敲低LACTB减少了NPC细胞的转移能力。但是，LACTB不会影响细胞增殖。我们进一步发现，LACTB在促进NPC转移中的作用取决于ERBB3 / EGFR-ERK信号的激活，进而激活了组蛋白H3的稳定性和随后的乙酰化。这些发现可能有助于揭示NPC转移的机制。