EN1 Regulates Cell Growth and Proliferation in Human Glioma Cells via Hedgehog Signaling.

Jinchun Chang,Runze Liu,Yuting Guo,Jianyu Li,Chenjia Guo,Song Huang,Zhangqian Liang,Jian Chen,Yankai Wang,Anliang Yu

doi:10.3390/ijms23031123

Abstract

Glioblastoma is an aggressive cancer of the nervous system that accounts for the majority of brain cancer-related deaths. Through cross-species transcriptome studies, we found that Engrailed 1 (EN1) is highly expressed in serum-free cultured glioma cells as well as glioma tissues, and increased expression level predicts a worse prognosis. EN1 controls glioma cell proliferation, colony formation, migration, and tumorigenic capacity in vivo. It also influences sensitivity of glioma cells to γ-ray irradiation by regulating intracellular ROS levels. Mechanistically, EN1 influences Hedgehog signaling by regulating the level of Gli1 as well as primary cilia length and the primary cilia transport-related protein TULP3. In conclusion, we demonstrate that EN1 acts as an oncogenic regulator that contributes to glioblastoma pathogenesis and could serve as a diagnostic/prognostic marker and therapeutic target for glioblastoma.

Highlights

Gliomas are the most common types of brain cancer, and glioblastoma is the most aggressive form of cancer that begins within the brain [1]
We found that the Engrailed gene was expressed at higher levels in mouse glioblastoma tumors than in normal tissues (Figure 1A), and it was mostly expressed by tumor cells (Figure S7)
Through cross-species transcriptome studies, we found that Engrailed 1 (EN1) is highly expressed in gliomas, that high expression of EN1 in gliomas affects cell proliferation, colony formation, and resistance to radiotherapy, as well as promoting tumor growth in vivo, and that EN1 may function as an oncogene in gliomas

Summary

Introduction

Gliomas are the most common types of brain cancer, and glioblastoma is the most aggressive form of cancer that begins within the brain [1]. The median survival of glioblastoma patients is generally 14–16 months, with fewer than 3–5% of patients surviving >5 years [3]. The standard treatment for glioblastoma is maximal safe resection followed by radiotherapy and chemotherapy with temozolomide [4]. In spite of intense efforts to optimize the treatment of gliomas over the past decades, no significant advancement in patient survival has been achieved. Glioblastoma is prone to chemotherapy and radiation resistance [5]

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Results

Conclusion