|
|||||
|
|
KRAS mutations upregulate Runx1 to promote occurrence of head and neck squamous cell carcinoma |
|
| Authors: | Miao Deng Jiaxin Guo Zihang Ling Chi Zhang Lihong He Zhaona Fan Bin Cheng Juan Xia |
| Affiliation: | 1. Hospital of Stomatology, Sun Yat-sen University, Guangzhou, P. R. China Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, P. R. China Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, P. R. China;2. Hospital of Stomatology, Sun Yat-sen University, Guangzhou, P. R. China |
| Abstract: | Gene mutations play an important role in head and neck squamous cell carcinoma (HNSCC) by not only promoting the occurrence and progression of HNSCC but also affecting sensitivity to treatment and prognosis. KRAS is one of the most frequently mutated oncogenes, which has been reported to have a mutation rate from 1.7% to 12.7% and may lead to poor prognosis in HNSCC, but its role remains unclear. Here, we found that the KRAS mutation can promote HNSCC generation through synergism with 4-Nitroquinoline-1-Oxide(4NQO). Mechanistically, KRAS mutations can significantly upregulate Runx1 to promote oral epithelial cell proliferation and migration and inhibit apoptosis. Runx1 inhibitor Ro 5-3335 can effectively inhibit KRAS-mutated HNSCC progression both in vitro and in vivo. These findings suggest that the KRAS mutation plays an important role in HNSCC and that Runx1 may be a novel therapeutic target for KRAS-mutated HNSCC. |
| Keywords: | animal model HNSCC KRAS Ro 5-3335 Runx1 |