Abstract 101: KPNA2 promotes the progression of lung adenocarcinoma

Abstract KPNA2 (Importin α1) is a nuclear transporter that mediates the nuclear import of proteins, such as transcription factors and nuclear proteins. Previous studies have highlighted KPNA2 as an important factor influencing CAF activity, prompting us to explore its role and mechanisms in the migration, invasion, and metastasis of lung cancer cells. Immunohistochemistry on tumor samples from lung cancer patients revealed that higher expression of KPNA2 was linked to poorer survival outcomes. To further investigate its function, we used shRNAs to knock down KPNA2 in human and mouse lung cancer cells. This led to a reduction in cancer cell migration, invasion, and metastasis. In contrast, overexpressing KPNA2 enhanced cancer cell migration and invasion. RNA sequencing analysis showed that KPNA2 regulates focal adhesion and NF-κB signaling pathways. Additionally, protein microarray analysis identified Golgi-associated and RNA-associated proteins as potential KPNA2-binding partners, which require further study. These results indicate that KPNA2 plays a crucial role in promoting cancer cell migration, invasion, and metastasis, making it a promising therapeutic target in lung adenocarcinoma. Citation Format: Seongran Cho, Inyoung Cheon, Seoree Kim, Yoon Ho Ko, Young-Ho Ahn. KPNA2 promotes the progression of lung adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 101.