Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan;166(1):113-127.
doi: 10.1007/s11060-023-04527-9. Epub 2024 Jan 8.

Endosome associated trafficking regulator 1 promotes tumor growth and invasion of glioblastoma multiforme via inhibiting TNF signaling pathway

Qian Zhang #  1 , Zhang'an Dai #  1 , Yingyu Chen  1 , Qun Li  1 , Yuhang Guo  1   2 , Zhangzhang Zhu  1 , Ming Tu  1 , Lin Cai  3 , Xianghe Lu  4
Affiliations

Endosome associated trafficking regulator 1 promotes tumor growth and invasion of glioblastoma multiforme via inhibiting TNF signaling pathway

Qian Zhang et al. J Neurooncol. 2024 Jan.

Abstract

Purpose: Endosome associated trafficking regulator 1 (ENTR1) is a novel endosomal protein, which can affect multiple cellular biological behavior by remodeling plasma membrane structures. However, little is known regarding its function and underlying mechanisms in glioblastoma multiforme.

Methods: Expression profile and clinical signature were obtained from The Public Database of human tumor. Immunohistochemical staining and western blotting assays were used to measure ENTR1 expression level. Human primary GBM tumor cells and human GBM cell lines A172, U87 and U251 were used to clarify the precise role of ENTR1. CCK-8 assays, wound healing and transwell invasion assays were designed to investigate cell viability, invasion and migration of GBM cells, respectively. Underlying molecular mechanisms of ENTR1 were determined via RNA-seq analysis. Tumor formation assay was used to validate the influence of ENTR1 in vivo.

Results: Compared with normal brain tissues, ENTR1 was highly expressed in gliomas and correlated with malignant grades of gliomas and poor overall survival time. The proliferation and invasion of GBM cells could be weaken and the sensitivity to temozolomide (TMZ) chemotherapy increased after knocking down ENTR1. Overexpression of ENTR1 could reverse this effect. RNA-seq analysis showed that tumor necrosis factor (TNF) signaling pathway might be a putative regulatory target of ENTR1. Tumor formation assay validated that ENTR1 was a significant factor in tumor growth.

Conclusion: Our results indicated that ENTR1 played an important role in cell proliferation, invasion and chemotherapeutic sensitivity of GBM, suggesting that ENTR1 might be a novel prognostic marker and significant therapeutic target for GBM.

Keywords: Endosome associated trafficking regulator 1; Glioblastoma; Invasion; Proliferation; Temozolomide; Tumor necrosis factor.

PubMed Disclaimer

References

    1. Poon M, Bruce M, Simpson J, Hannan C, Brennan P (2021) Temozolomide sensitivity of malignant glioma cell lines—a systematic review assessing consistencies between in vitro studies. BMC Cancer 21(1):1240. https://doi.org/10.1186/s12885-021-08972-5 - DOI - PubMed - PMC
    1. Pająk B (2022) Looking for the holy grail-drug candidates for glioblastoma multiforme chemotherapy. Biomedicines 10(5):1001. https://doi.org/10.3390/biomedicines10051001 - DOI - PubMed - PMC
    1. Caccese M, Simonelli M, Villani V, Rizzato S, Ius T, Pasqualetti F et al (2022) Definition of the prognostic role of MGMT promoter methylation value by pyrosequencing in newly diagnosed IDH wild-type glioblastoma patients treated with radiochemotherapy: a large multicenter study. Cancers 14(10):2425. https://doi.org/10.3390/cancers14102425 - DOI - PubMed - PMC
    1. Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352(10):997–1003. https://doi.org/10.1056/NEJMoa043331 - DOI - PubMed
    1. Hegi ME, Genbrugge E, Gorlia T, Stupp R, Gilbert MR, Chinot OL et al (2019) MGMT promoter methylation cutoff with safety margin for selecting glioblastoma patients into trials omitting temozolomide: a pooled analysis of four clinical trials. Clin Cancer Res 25(6):1809–1816. https://doi.org/10.1158/1078-0432.CCR-18-3181 - DOI - PubMed

Substances

LinkOut - more resources