1. School of Chemistry and Chemical Engineering & Zhongda Hospital, School of Medicine, Advanced Institute for Life and Health, Southeast University, Nanjing 210096, China.
2. The Translational Research Institute for Neurological Disorders, Department of Neurosurgery, the First Affiliated Hospital (Yijishan Hospital), Wannan Medical College, Wuhu 241000, China.
3. Department of Gynecologic Oncology, Cancer Hospital of Shantou University Medical College, Shantou 515041, China.
4. Department of Pathology, Nanjing Drum Tower Hospital Clinical College & Key Laboratory of Antibody Technique of National Health Commission & Jiangsu Antibody Drug Engineering Research Center, Nanjing Medical University, Nanjing, China.
5. Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University (Army Medical University) and Key Laboratory of Tumor Immunopathology, Ministry of Education of China, Chongqing, 400038, China.
6. Department of Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research, Nanjing 210009, China.
# These authors contributed equally.
Objective: Secreted and transmembrane protein 1 (SECTM1) is a gene encoding a transmembrane protein. The role of SECTM1 in glioblastoma (GBM) is unclear. Here, we reported the abnormal expression of SECTM1 in GBM for the first time and studied the role and mechanism of SECTM1 in GBM.
Methods: qRT-PCR, Western blotting and immunofluorescence were used to detect the expression of SECTM1 in gliomas of different grades and GBM cell lines. After the knockdown of SECTM1 expression in cell lines by shRNA, the effect of SECTM1 in GBM cell lines was verified by CCK-8, Transwell, EdU and wound healing experiments. We further investigated the effect and mechanism of SECTM1 on GBM in vitro and in vivo. The effect of SECTM1 on glioma growth was detected by subcutaneous tumor xenografts in nude mice in vivo.
Results: The results showed that the knockdown of SECTM1 expression in cell lines significantly inhibited the proliferation, migration and invasion of GBM cells while inhibiting the progression of subcutaneous xenograft tumors in nude mice. However, the role and molecular mechanism of SECTM1 in GBM remain unclear. SECTM1 was found to promote GBM epithelial-mesenchymal transition (EMT) like processes. Bioinformatics analysis and Western blotting showed that SECTM1 regulates glioblastoma invasion and EMT-like processes mainly through the TGFβ1/Smad signaling pathway.
Conclusion: The low expression of SECTM1 has an inhibitory effect on GBM and is a potential target for GBM treatment. SECTM1 may also be a promising biomarker for the diagnosis and prognosis of GBM.
Keywords: SECTM1, glioblastoma, invasion, EMT