星形细胞上调基因-1 通过 p65 磷酸化和 MMP1 的上调与头颈部鳞状细胞癌的转移有关。

BACKGROUND

The survival rate of head and neck squamous cell carcinoma (HNSCC) at advanced stage is poor, despite contemporary advances in treatment modalities. Recent studies have indicated that astrocyte elevated gene-1 (AEG-1), a single transmembrane protein without any known functional domains, is overexpressed in various malignancies and is implicated in both distant metastasis and poor survival.

RESULTS

High expression of AEG-1 in HNSCC was positively correlated with regional lymph node metastasis and a poor 5-year survival rate. Knockdown of AEG-1 in HNSCC cell lines reduced their capacity for colony formation, migration and invasion. Furthermore, decreased tumor volume and metastatic foci were observed after knockdown of AEG-1 in subcutaneous xenografts and pulmonary metastasis assays in vivo, respectively. We also demonstrated that AEG-1 increased phosphorylation of the p65 subunit of NF-κB, and regulated the expression of MMP1 in HNSCC cells. Moreover, compromised phosphorylation of the p65 (RelA) subunit of NF-κB at serine 536 was observed upon silencing of AEG-1 in both HNSCC cell lines and clinical specimens.

CONCLUSION

High expression of AEG-1 is associated with lymph node metastasis and its potentially associated mechanism is investigated.

背景

尽管当代治疗方法取得了进展，但头颈部鳞状细胞癌（HNSCC）晚期的生存率仍然很差。最近的研究表明，星形细胞上调基因-1（AEG-1）在各种恶性肿瘤中过表达，它是一种没有任何已知功能域的单一跨膜蛋白，与远处转移和不良预后有关。

结果

AEG-1 在 HNSCC 中的高表达与区域淋巴结转移和 5 年生存率差呈正相关。在 HNSCC 细胞系中敲低 AEG-1 可降低其集落形成、迁移和侵袭能力。此外，在体内皮下异种移植和肺转移实验中敲低 AEG-1 后，肿瘤体积和转移灶均减少。我们还证明 AEG-1 可增加 NF-κB p65 亚基的磷酸化，并调节 HNSCC 细胞中 MMP1 的表达。此外，在 HNSCC 细胞系和临床标本中沉默 AEG-1 后，观察到 NF-κB p65（RelA）亚基丝氨酸 536 的磷酸化受损。