Category: Id-1

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ID1 Is Critical for Tumorigenesis and Regulates Chemoresistance in Glioblastoma

Abstract

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, these data suggest ID1 could be a promising therapeutic target in patients with glioblastoma. SIGNIFICANCE: These findings show that the transcriptional regulator ID1 is critical for glioblastoma initiation and chemoresistance and that inhibition of ID1 enhances the effect of temozolomide, delays tumor recurrence, and prolongs survival.

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Id-1 is a Key Transcriptional Regulator of Glioblastoma Aggressiveness and a Novel Therapeutic Target

Abstract

Glioblastoma (GBM) is the most common form of primary adult brain tumors. A majority of GBMs grow invasively into distant brain tissue, leading to tumor recurrence, which is ultimately incurable. It is, therefore, essential to discover master regulators that control GBM invasiveness and target them therapeutically. We demonstrate here that the transcriptional regulator Id-1 plays a critical role in modulating the invasiveness of GBM cell lines and primary GBM cells. Id-1 expression levels positively correlate with glioma cell invasiveness in culture and with histopathological grades in patient biopsies. Id-1 knockdown dramatically reduces GBM cell invasion that is accompanied by profound morphological changes and robust reduction in expression levels of “mesenchymal” markers, as well as inhibition of self-renewal potential and down-regulation of glioma stem cell markers. Importantly, genetic knockdown of Id-1 leads to a significant increase in survival in an orthotopic model of human GBM. Furthermore, we show that a non-toxic compound, cannabidiol, significantly down-regulates Id-1 gene expression and associated glioma cell invasiveness and self-renewal. Additionally, cannabidiol significantly inhibits the invasion of GBM cells through an organotypic brain slice and glioma progression in vivo. Our results suggest that Id-1 regulates multiple tumor-promoting pathways in GBM, and that drugs targeting Id-1 represent a novel and promising strategy for improving the therapy and outcome of GBM patients.

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Id-1: Regulator of EGFR and VEGF and potential target for colorectal cancer therapy

This study revealed that Id-1, EGFR and VEGF took part in development and progression of colorectal carcinomas and that Id-1 was associated with regulations of EGFR and VEGF. The results of this study support the idea that not only EGFR and VEGF but also Id-1 could be new targets in cancer treatment.

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Expression of the inhibitor of DNA-binding (ID)-1 protein as an angiogenic mediator in tumour advancement of uterine cervical cancers

Abstract [CONDENSED]

…the 36-month survival rate of patients with high ID-1 was poor (60%), whereas that of the patients with low ID-1 was significantly higher (83%). ID-1 correlated with microvessel counts in uterine cervical cancers. ID-1 expression also correlated significantly with histoscore. Therefore, ID-1 might work on tumour advancement through angiogenic activity and is considered to be a candidate for a prognostic indicator in uterine cervical cancers.

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Overexpression of Id-1 protein is a marker in colorectal cancer progression

Abstract

The inhibitor of differentiation/DNA binding 1 (Id-1), a negative regulator of basic helix-loop-helix transcription factors, plays an important role in the regulation of cell proliferation and differentiation. We examined the Id-1 expression by immunohistochemistry in 9 adenomas, 79 primary colorectal adenocarcinomas matched with 40 adjacent normal mucosa specimens and its relationship with clinicopathological factors. The Id-1 expression was increased in the carcinoma compared to the adjacent normal mucosa either in the unmatched and matched samples or to the adenoma. There was no significant difference in the Id-1 expression between normal mucosa and adenoma. The Id-1 expression of carcinoma was increased from Dukes’ stages A to B, to C and to D. The cases with lymph node metastasis had a higher rate of a stronger Id-1 expression than those without lymph node metastasis. In conclusion, Id-1 overexpression plays an important role in colorectal cancer progression.

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Level of Id-1 Protein Expression Correlates with Poor Differentiation, Enhanced Malignant Potential, and More Aggressive Clinical Behavior of Epithelial Ovarian Tumors

Abstract [condensed]

Strong or moderate expression of Id-1 was a strong predictor for shorter overall survival. The level of Id-1 protein expression correlates with the malignant potential of ovarian tumors. In cancer samples, stronger Id-1 expression is associated with poor differentiation and more aggressive behavior of tumor cells, resulting in poor clinical outcome. Consequently, Id-1 inhibition in the future might be of benefit for patients with ovarian cancer.

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Overexpression of Id-1 Protein Is a Marker for Unfavorable Prognosis in Early-Stage Cervical Cancer

Abstract [condensed]

We investigated the prognostic influence of Id-1 expression in 89 patients with cervical cancer. patients with strong or moderate expression of Id-1 had a significant shorter overall survival time and disease-free survival time compared with those with low or absent Id-1 expression. Id-1 expression is an independent prognostic marker in early-stage cervical cancer.

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