TMED2 promotes glioma tumorigenesis by being involved in EGFR recycling transport

• Published in: International journal of biological macromolecules 2024-03, Vol.262 (Pt 2), p.130055, Article 130055
• Main Authors: Sun, Changning, Zhang, Yihan, Wang, Zhuangzhi, Chen, Jin, Zhang, Junhua, Gu, Yuchao
• Format: Article
• Language: English
• Subjects: Animals; carcinogenesis; Carcinogenesis - genetics; Cell Line, Tumor; Cell Proliferation; Cell Transformation, Neoplastic; domain; EGFR; EGFR recycling; endoplasmic reticulum; epidermal growth factor receptors; ErbB Receptors - metabolism; Glioma; Glioma - drug therapy; Golgi apparatus; Mice; protein transport; Signal Transduction; therapeutics
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.130055

Aberrant epidermal growth factor receptor (EGFR) signaling is the core signaling commonly activated in glioma. The transmembrane emp24 protein transport domain protein 2 (TMED2) interacts with cargo proteins involved in protein sorting and transport between endoplasmic reticulum (ER) and Golgi apparatus. In this study, we found the correlation between TMED2 with glioma progression and EGFR signaling through database analysis. Moreover, we demonstrated that TMED2 is essential for glioma cell proliferation, migration, and invasion at the cellular levels, as well as tumor formation in mouse models, underscoring its significance in the pathobiology of gliomas. Mechanistically, TMED2 was found to enhance EGFR-AKT signaling by facilitating EGFR recycling, thereby providing the initial evidence of TMED2's involvement in the membrane protein recycling process. In summary, our findings shed light on the roles and underlying mechanisms of TMED2 in the regulation of glioma tumorigenesis and EGFR signaling, suggesting that targeting TMED2 could emerge as a promising therapeutic strategy for gliomas and other tumors associated with aberrant EGFR signaling. •High expression of TMED2 in glioma is positively related to the progression of glioblastoma and poor outcomes.•High expression of TMED2 is positively related to EGFR-AKT signaling.•TMED2 promotes glioblastoma tumorigenesis in vitro and in vivo by regulating the EGFR-AKT signaling.•TMED2's facilitation of EGFR recycling supports its involvement in protein recycling and enhances EGFR-AKT signaling.