1. GCC2 promotes non-small cell lung cancer progression by maintaining Golgi apparatus integrity and stimulating EGFR signaling pathways
- Author
-
Min Sang Kim, Hyesun Jeong, Byeong Hyeon Choi, Jiho Park, Gun Seop Shin, Jik-Han Jung, Hyunku Shin, Ka-Won Kang, Ok Hwa Jeon, Jewon Yu, Ji-Ho Park, Yong Park, Yeonho Choi, Hyun Koo Kim, and Sunghoi Hong
- Subjects
GRIP and coiled-coil domain containing 2 (GCC2) ,Non-small cell lung cancer (NSCLC) ,Exosomes ,Cancer growth signaling ,Golgi apparatus ,Medicine ,Science - Abstract
Abstract Fundamental changes in intracellular processes, such as overactive growth signaling pathways, are common in carcinomas and are targets of many cancer therapeutics. GRIP and coiled-coil containing 2 (GCC2) is a trans-Golgi network (TGN) golgin maintaining Golgi apparatus structure and regulating vesicle transport. Here, we found an aberrant overexpression of GCC2 in non-small cell lung cancer (NSCLC) and conducted shRNA-mediated gene knockdown to investigate the role of GCC2 in NSCLC progression. shRNA-mediated GCC2 knockdown suppressed NSCLC cell growth, migration, stemness, and epithelial-mesenchymal transition (EMT) in vitro and tumor growth in vivo. In addition, GCC2 knockdown suppressed cancer cell exosome secretion and the oncogenic capacity of cancer cell-derived exosomes. Mechanistically, GCC2 inhibition decreased epidermal growth factor receptor (EGFR) expression and downstream growth and proliferation signaling. Furthermore, GCC2 inhibition compromised Golgi structural integrity in cancer cells, indicating a functional role of GCC2 in regulating intracellular trafficking and signaling to promote lung cancer progression. Together, these findings suggest GCC2 as a potential therapeutic target for the treatment of NSCLC.
- Published
- 2024
- Full Text
- View/download PDF