IGFBP2: integrative hub of developmental and oncogenic signaling network

Li, Tao; Forbes, M. Elizabeth; Fuller, Gregory N.; Li, Jiabo; Yang, Xuejun; Zhang, Wei

doi:10.1038/s41388-020-1154-2

Cited by 110 publications

(82 citation statements)

References 164 publications

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“…Upregulation of the KRAS pathway is expected in a tumor such as MEL1 that is mutant in NF1, which functions as a RAS GTPase-activating protein (GAP) (Cirenajwis et al, 2017). The insulin-like growth factor receptor IGF-1R and the IGF binding protein IGFBP2, which is a mitogenic factor in multiple cancers (Li et al, 2020), were significantly upregulated in EM relative to IM. BCL2A1 (Haq et al, 2013), an antiapoptotic pro-survival member of the BCL2 gene family, was another gene upregulated in IM relative to EM (Figure 2L).…”

Section: Multimodal Profiling Of Spatially Distinct Regions Within Cutaneous Melanomamentioning

confidence: 99%

The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution

Nirmal

Maliga

Vallius

et al. 2021

Preprint

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Cutaneous melanoma is a highly immunogenic disease, surgically curable at early stages, but life-threatening when metastatic. Here we integrate high-plex imaging, 3D high-resolution microscopy, and spatially-resolved micro-region transcriptomics to study immune evasion and immunoediting in primary melanoma. We find that recurrent cellular neighborhoods involving tumor, immune, and stromal cells change significantly along a progression axis from precursor states to melanoma in situ to invasive tumor. Hallmarks of immunosuppression are detectable by the precursor stage, and when tumors become locally invasive, a consolidated and spatially restricted suppressive environment forms along the tumor-stromal boundary. This environment is established by cytokine gradients that promote expression of MHC-II and IDO1 and by PDL1-expressing macrophages and dendritic cells engaging activated T cells. However, a few mm away, T cells synapse with melanoma cells in fields of tumor regression. Thus, invasion and immunoediting can co-exist within a few millimeters of each other in a single specimen.

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Section: Multimodal Profiling Of Spatially Distinct Regions Within Cutaneous Melanomamentioning

confidence: 99%

The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution

Nirmal

Maliga

Vallius

et al. 2021

Preprint

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“…It was confirmed that the abnormal expression of CYP24A1 was related to cancer risk and might contribute to tumor aggressiveness ( Hu et al, 2019 ; King et al, 2010 ). Growing evidence indicates that IGFBP2 plays an essential role in several key oncogenic processes, such as tumor cellular proliferation, epithelial to mesenchymal transition, stemness, invasion, angiogenesis, immunoregulation, and migration ( Li et al, 2020 ). In our signature, CD36, ELL, and MPC1 are important genes associated with CRC prognosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of Vitamin D-related gene signature to predict colorectal cancer prognosis

Huang

et al. 2021

PeerJ

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Colorectal cancer (CRC) is one of the most common malignant carcinomas worldwide with poor prognosis, imposing an increasingly heavy burden on patients. Previous experiments and epidemiological studies have shown that vitamin D and vitamin D-related genes play a vital role in CRC. Therefore, we aimed to construct a vitamin D-related gene signature to predict prognosis in CRC. The CRC data from The Cancer Genome Atlas (TCGA) was performed as the training set. A total of 173 vitamin D-related genes in the TCGA CRC dataset were screened, and 17 genes associated with CRC prognosis were identified from them. Then, a vitamin D-related gene signature consisting of those 17 genes was established by univariate and multivariate Cox analyses. Moreover, four external datasets (GSE17536, GSE103479, GSE39582, and GSE17537) were used as testing set to validate the stability of this signature. The high-risk group presented a significantly poorer overall survival than low-risk group in both of training set and testing sets. Besides, the areas under the curve (AUCs) for signature on OS in training set at 1, 3, and 5 years were 0.710, 0.708, 0.710 respectively. The AUCs of the ROC curve in GSE17536 for 1, 3, and 5 years were 0.649, 0.654, and 0.694. These results indicated the vitamin D-related gene signature model could effectively predict the survival status of CRC patients. This vitamin D-related gene signature was also correlated with TNM stage in CRC clinical parameters, and the higher risk score from this model was companied with higher clinical stage. Furthermore, the high accuracy of this prognostic signature was validated and confirmed by nomogram model. In conclusion, we have proposed a novel vitamin D-related gene model to predict the prognosis of CRC, which will help provide new therapeutic targets and act as potential prognostic biomarkers for CRC.

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“…PTEN, a tumor suppressor, acts as a checkpoint in IGFBP2 signalling cascade. "IGFBP2 is the most significant marker of PTEN loss and AKT activation" in glioblastoma 34 .Both exogenous and cellular IGFBP2 overexpression lead to activation of STAT3 35 .IGFBP2 potentiates STAT3 by activation of nuclear EGFR signalling pathway 35 . "STAT3 and NF-κB are said to be the two major downstream transcriptional factors of IGFBP2 that direct tumorigenic" intracellular signalling 35 .Finally, IGFBP2 is capable of nuclear translocation 36 and is involved transcriptional regulation of the VEGF gene and modulates angiogenesis 36 .…”

Section: Discussionmentioning

confidence: 99%

IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme

KP¹,

Wlochowitz²,

Wingender³

et al. 2020

Preprint

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Only 2% of Glioblastoma multiforme (GBM) patients respond to standard care and survive beyond 36 months (long-term survivors, LTS) while the majority survives less than 12 months (short-term survivors, STS). To understand the mechanism leading to poor survival, we analyzed publicly available datasets of 113 STS and 58 LTS. This analysis revealed 198 differentially expressed genes (DEGs) that co-occur with aggressive tumor growth and may be responsible for the poor prognosis. These genes belong largely to the GO-categories “epithelial to mesenchymal transition” and “response to hypoxia”. Promoter and network analysis of the DEGs identified 5 potential master regulators that may explain dysregulation of the DEGs in the STS. The following 5 important master-regulators were identified: IGFBP2, VEGFA, PDGFA, OSMR and AEBP1. It is known that IGFBP2 confers increasing malignancy leading to poor prognosis. However, the molecular mechanism by which IGFBP2 affects disease progression and patient prognosis is unclear. Here we found that IGFBP2 is highly upregulated in short survivors and significantly impact survival. Further investigation of the gene regulatory network revealed that IGFBP2 expression can be regulated by FRA-1 transcription factor via MEK2/RAF/ERK5 pathway. FRA-1 is found to be upregulated and to have significant impact on survival in GBM. It is previously reported that FRA-1 can dysregulate at-least 50 genes involved in tumor invasiveness in tumor xenografts making it a therapeutic target for GBM intervention. We propose that IGFBP2 drives dysregulated gene network responsible for short survival in GBM via FRA-1 transcription factor.

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IGFBP2: integrative hub of developmental and oncogenic signaling network

Cited by 110 publications

References 164 publications

The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution

The spatial landscape of progression and immunoediting in primary melanoma at single cell resolution

Identification of Vitamin D-related gene signature to predict colorectal cancer prognosis

IGFBP2 is a Potential Master-Regulator Driving Dysregulated Gene Network Responsible for Short Survival in Glioblastoma Multiforme

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