Epithelial membrane protein 1 promotes glioblastoma progression through the PI3K/AKT/mTOR signaling pathway

Abstract

Glioblastoma multiforme (GBM) is the most malignant intracranial tumor. Although the affected patients are usually treated with surgery combined with radiotherapy and chemotherapy, the median survival time for GBM patients is still approximately 12–14 months. Identifying the key molecular mechanisms and targets of GBM development may therefore lead to the development of improved therapies for GBM patients. In the present study, the clinical significance and potential function of epithelial membrane protein 1 (EMP1) in malignant gliomas were investigated. Increased EMP1 expression was associated with increasing tumor grade (P<0.001) and worse prognosis in patients (P<0.001) based on TCGA, Rembrandt and CGGA databases for human gliomas. In vitro , gene silencing of EMP1 in U87MG and P3 GBM (primary glioma) cells significantly inhibited tumor proliferation and invasion. In addition, it was revealed that activation of the PI3K/AKT/mTOR signaling pathway is the driving force of EMP1-promoted glioma progression. Finally, it was demonstrated, using an intracranial GBM animal model, that EMP1 knockdown significantly inhibits tumor growth in vivo and increases overall survival in tumor-bearing animals. Our research provides new insights into the molecular mechanisms underlying EMP1 knockdown-mediated inhibition of GBM cell invasion and raises the possibility that targeting of EMP1 may represent a promising strategy for the treatment of GBM.

The prognostic value of six survival-related genes in bladder cancer

“…The six survival-related genes, which were the basis for clustering, played a negative role in the survival of patients. This is in accordance with the previously reported studies of these genes 6 – 11 .…”

“…All six selected survival-related genes (EMP1, TPM1, NRP2, FGFR1, CAVIN1, and LATS2) were reported to play a positive role in disseminating cancer cells or invasion in many kinds of cancers [6][7][8][9][10][11] . EMP1 belongs to the peripheral myelin protein 22-kDa (PMP22) gene family.…”

“…EMP1 belongs to the peripheral myelin protein 22-kDa (PMP22) gene family. It promotes glioblastoma progression through the PI3K/AKT/mTOR signaling pathway 6 , and the unusual expression of EMP1 has been revealed in most tumor types 12 . TPM1 gene is a member of a tumor-associated protein family (the tropomyosin family) -it plays an important role in tumor-specific variations of actin filament aggregation via stress fiber modulation and actin cytoskeleton modification 7 .…”

Targeting Glutamine Addiction in Gliomas

“…The oversupply of glucose and increased aerobic glycolysis (Warburg effect) result from oncogenic mutations. The stabilization of HIF-1α, p53 loss, upregulation of PI3K and its downstream AKT kinase and mTOR pathway, and overexpression of c-Myc transcription factor are the basic mechanisms of genetic adaptations of brain neoplasms leading to glycolysis enhancement and glucose addiction [49][50][51][52][53]. The c-Myc transcription factor's overexpression in 293T and U87MG GBM cell lines resulted in increased levels of glycolytic intermediates (glucose-and fructose-6-phosphate, pyruvate, lactate) and decreased cell viability in glucose-free media.…”

<p>EMP1 Promotes the Proliferation and Invasion of Ovarian Cancer Cells Through Activating the MAPK Pathway</p>

“…12,13 Li et al found that in glioblastoma, highly expressed EMP1 promotes tumor cell proliferation, invasion and metastasis by activating PI3K/AKT/mTOR signaling pathway. 14 Ogita et al found that EMP1 binding with copine-III promoted the expression of Src, Vav2 and Rac1 in prostate cancer, leading to enhanced migration and metastasis of prostate cancer cells, indicating that EMP1 may take a part in the positive regulation of metastasis. 15 Boer et al found that EMP1 is elevated in childhood acute lymphoblastic leukemia.…”