School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Department of Otolaryngology Head and Neck Surgery, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Carcinogenesis. 2021 Apr 17;42(3):414-422. doi: 10.1093/carcin/bgaa116.
Tumor progression and metastasis are still major burdens for head and neck squamous cell carcinoma (HNSCC). Runt-related transcription factor 1 (RUNX1) is involved in aggressive phenotypes in several cancers, while the molecular role of RUNX1 underlying cancer progression and metastasis of HNSCC remains largely unknown. In our study, RUNX1 expression was increased with disease progression in patients with HNSCC. The silencing of RUNX1 significantly decelerated the malignant progression of HNSCC cells, reduced osteopontin (OPN) expression in vitro and weakened the tumorigenicity of HNSCC cells in vivo. Moreover, we demonstrated that RUNX1 activated the mitogen-activated protein kinase signaling by directly binding to the promoter of OPN in tumor progression and metastasis of HNSCC. Our results may provide new insight into the mechanisms underlying the role of RUNX1 in tumor progression and metastasis and reveal the potential therapeutic target in HNSCC.
肿瘤的进展和转移仍然是头颈部鳞状细胞癌(HNSCC)的主要负担。 runt 相关转录因子 1(RUNX1)参与了几种癌症的侵袭性表型,而 RUNX1 在 HNSCC 肿瘤进展和转移中的分子作用在很大程度上仍然未知。在我们的研究中,RUNX1 的表达随着 HNSCC 患者疾病的进展而增加。RUNX1 的沉默显著减缓了 HNSCC 细胞的恶性进展,减少了体外骨桥蛋白(OPN)的表达,并减弱了 HNSCC 细胞在体内的致瘤性。此外,我们证明 RUNX1 通过直接结合 OPN 启动子在 HNSCC 的肿瘤进展和转移中激活丝裂原活化蛋白激酶信号通路。我们的研究结果可能为 RUNX1 在肿瘤进展和转移中的作用机制提供新的见解,并揭示 HNSCC 潜在的治疗靶点。