RASSF9 promotes NSCLC cell proliferation by activating the MEK/ERK axis

• Main Authors: Jun Yuan, Qianqian Ju, Jun Zhu, Yun Jiang, Xuechao Yang, Xiaoyu Liu, Jinyu Ma, Cheng Sun, Jiahai Shi
• Format: Article
• Language: English
• Published: Nature Publishing Group 2021-07-01
• Series: Cell Death Discovery
• Online Access: https://doi.org/10.1038/s41420-021-00583-0

Abstract The RAS-associated domain family 9 (RASSF9), a RAS-associated domain family gene, is expressed in a variety of tissues. However, its roles in tumorigenesis, particularly in non-small cell lung cancer (NSCLC), are still not understood well. In the present study, we aimed to examine the potential roles of RASSF9 in NSCLC and the underlying mechanisms. Our data showed that RASSF9 expression was upregulated in NSCLC tissues and cell lines. Increased expression of RASSF9 promotes NSCLC cell proliferation. On the contrary, knockdown of RASSF9 represses cell proliferation. Moreover, the effects of RASSF9 on NSCLC cell proliferation were further confirmed in vivo by using a subcutaneous tumor model. Mechanistically, pharmacological intervention studies revealed that the MEK/ERK axis is targeted by RASSF9 for transducing its regulatory roles on NSCLC cell proliferation. Collectively, our data indicate that RASSF9 plays a key role in tumorigenesis of NSCLC by stimulating tumor cell proliferation, which relies on activation of the MEK/ERK axis. Thus, RASSF9 might be a druggable target for developing novel agents for treating NSCLC.