ID1 in glioblastoma

Glioblastoma is the most common primary brain tumor in adults. While the introduction of temozolomide chemotherapy has increased long-term survivorship, treatment failure and rapid tumor recurrence remains universal. The transcriptional regulatory protein, inhibitor of DNA-binding-1 (ID1), is a key regulator of cell phenotype in cancer. We show that CRISPR-mediated knockout of ID1 in glioblastoma cells, breast adenocarcinoma cells, and melanoma cells, dramatically reduced tumor progression in all three cancer systems through transcriptional downregulation of EGF, which resulted in decreased EGFR phosphorylation. Moreover, ID1-positive cells were enriched by chemotherapy and drove tumor recurrence in glioblastoma. Addition of the neuroleptic drug pimozide to inhibit ID1 expression enhanced the cytotoxic effects of temozolomide therapy on glioma cells and significantly prolonged time to tumor recurrence. Conclusively, this data suggests ID1 could be a promising therapeutic target in patients with glioblastoma.EGA study EGAS00001003711

胶质母细胞瘤（Glioblastoma）是成人最常见的原发性脑肿瘤。尽管替莫唑胺（temozolomide）化疗的应用提升了患者的长期生存率，但治疗失败与肿瘤快速复发仍是普遍存在的临床难题。转录调控蛋白DNA结合抑制因子1（ID1）是癌症细胞表型的关键调控因子。本研究证实，在胶质母细胞瘤细胞、乳腺腺癌细胞与黑色素瘤细胞中通过CRISPR介导敲除ID1，可通过转录下调表皮生长因子（EGF），进而降低表皮生长因子受体（EGFR）磷酸化水平，最终显著抑制三种癌症体系的肿瘤进展。此外，化疗会富集ID1阳性细胞，并驱动胶质母细胞瘤的肿瘤复发。使用抗精神病药物匹莫齐特（pimozide）抑制ID1表达，可增强替莫唑胺对神经胶质瘤细胞的细胞毒性作用，并显著延长肿瘤复发时间。综上，本研究数据表明ID1有望成为胶质母细胞瘤患者的潜在治疗靶点。本数据集隶属于欧洲基因组-表型组档案库（EGA），编号为EGAS00001003711。