GCC2 promotes non-small cell lung cancer progression by maintaining Golgi apparatus integrity and stimulating EGFR signaling pathways.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Carcinoma, Non-Small-Cell Lung*/metabolism ; Carcinoma, Non-Small-Cell Lung*/pathology ; Carcinoma, Non-Small-Cell Lung*/genetics ; ErbB Receptors*/metabolism ; ErbB Receptors*/genetics ; Signal Transduction* ; Lung Neoplasms*/metabolism ; Lung Neoplasms*/pathology ; Lung Neoplasms*/genetics ; Golgi Apparatus*/metabolism ; Cell Proliferation* ; Disease Progression*; Humans ; Animals ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/genetics ; Mice ; Cell Movement/genetics ; Golgi Matrix Proteins/metabolism ; Golgi Matrix Proteins/genetics ; Gene Expression Regulation, Neoplastic ; Exosomes/metabolism ; Exosomes/genetics

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.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)

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2019M3E5D5065399 Ministry of Science and ICT, South Korea; 2019M3E5D5065399 Ministry of Science and ICT, South Korea; 2019M3E5D5065399 Ministry of Science and ICT, South Korea; 2019M3E5D5065399 Ministry of Science and ICT, South Korea; 2019M3E5D5065399 Ministry of Science and ICT, South Korea; NRF-2020R1A2C1101294 National Research Foundation of Korea; NRF-2020R1A2C1101294 National Research Foundation of Korea; NRF-2020R1A2C1101294 National Research Foundation of Korea; NRF-2020R1A2C1101294 National Research Foundation of Korea; NRF-2020R1A2C1101294 National Research Foundation of Korea; RS-2022-00060247 Ministry of Health and Welfare; RS-2022-00060247 Ministry of Health and Welfare; RS-2022-00060247 Ministry of Health and Welfare; RS-2022-00060247 Ministry of Health and Welfare; RS-2022-00060247 Ministry of Health and Welfare

Keywords: Cancer growth signaling; Exosomes; GRIP and coiled-coil domain containing 2 (GCC2); Golgi apparatus; Non-small cell lung cancer (NSCLC)

EC 2.7.10.1 (ErbB Receptors)
EC 2.7.10.1 (EGFR protein, human)
0 (Golgi Matrix Proteins)

Date Created: 20241121 Date Completed: 20241121 Latest Revision: 20241125

20250114

PMC11582359

10.1038/s41598-024-75316-1

39572606