Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells

Fakhraldeen, Saja A.; Clark, Rod J.; Roopra, Avtar; Chin, Emily; Huang, Wei; Castorino, John J.; Wisinski, Kari B.; Kim, TaeWon; Spiegelman, Vladimir S.; Alexander, Caroline M.

doi:10.1074/jbc.m115.655175

Cited by 48 publications

(59 citation statements)

References 52 publications

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“…While it has been appreciated that mRNA-binding proteins including IMP1, Lin28b, and Musashi are increased in epithelial tumor cells, it is not yet known if these factors play a role in the tumor microenvironment (10–13). Imp1- hypomorphic mice exhibit dwarfism, decreased organ size, morphologically defective intestines, and death near birth for a large portion of mice (14, 15). Recent studies demonstrated a specific role for IMP1 to promote expansion of fetal neural stem cells via post-transcriptional enhancement of self-renewal gene products including Hmga2 (16).…”

Section: Introductionmentioning

confidence: 99%

Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon

Hamilton

Chatterji

Lundsmith

et al. 2015

Molecular Cancer Research

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The colon tumor microenvironment (TME) is becoming increasingly recognized as a complex but central player in the development of many cancers. Previously, we identified an oncogenic role for the mRNA-binding protein IMP1 (IGF2BP1) in the epithelium during colon tumorigenesis. In the current study, we reveal the contribution of stromal IMP1 in the context of colitis-associated colon tumorigenesis. Interestingly, stromal deletion of Imp1 (Dermo1Cre;Imp1LoxP/LoxP, or Imp1ΔMes) in the azoxymethane/dextran sodium sulfate (AOM/DSS) model of colitis-associated cancer resulted in increased tumor numbers of larger size and more advanced histological grade than controls. In addition, Imp1ΔMes mice exhibited a global increase in pro-tumorigenic microenvironment factors, including enhanced inflammation and stromal components. Evaluation of purified mesenchyme from AOM/DSS-treated Imp1ΔMes mice demonstrated an increase in hepatocyte growth factor (HGF), which has not been associated with regulation via IMP1. Genetic knockdown of Imp1 in human primary fibroblasts confirmed an increase in HGF with Imp1 loss, demonstrating a specific, cell-autonomous role for Imp1 loss to increase HGF expression. Taken together, these data demonstrate a novel tumor-suppressive role for IMP1 in colon stromal cells and underscore an exquisite, context-specific function for mRNA-binding proteins, such as IMP1, in disease states.

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Section: Introductionmentioning

confidence: 99%

Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon

Hamilton

Chatterji

Lundsmith

et al. 2015

Molecular Cancer Research

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“…In addition, GHET1 have been shown to directly interact with insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) and have increased the physical interface between MYC mRNA and IGF2BP1 (18). Considering the role of GHET1 in regulation of MYC mRNA stability and expression via its interaction with IGF2BP1 (18), frequent MYC dysregulation in breast cancer (20) as well as expression of IGF2BP1 in breast cancer and its role in clonogenic growth of these cells (21), GHET1 was expected to participate in breast cancer pathogenesis as well. However, the results of the present study showed no consistent expression trend in samples with breast cancer examined.…”

Section: Discussionmentioning

confidence: 99%

Long non-coding RNA GHET1 Is Possibly Involved in the Pathogenesis of a Fraction of Breast Cancers

et al. 2017

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Background: Breast cancer is the most frequently diagnosed cancer among women. Although several targeted therapies have been applied for patients with breast cancer, due to its heterogeneous nature, several patients do not benefit from these treatment modalities. Consequently, it is necessary to identify novel markers, which participate in the development of breast cancer. Recently, long non-coding RNAs (lncRNAs) have gained attention in this regard. Among them is lncRNA-gastric carcinoma high expressed transcript 1 (lncRNA-GHET1), whose participation in gastric and bladder cancers have been identified. Objectives: In the present study, we aimed at identifying lncRNA-GHET1 expression in breast cancer tissues compared with their adjacent non-cancerous tissues (ANCT) in a cohort of Iranian patients. Methods: We evaluated the expression of GHET1 in 47 samples of invasive ductal carcinoma of breast in comparison with their ANCTs by means of quantitative real time-PCR. Results: GHET1 has been shown to be up-regulated in 26% (13 out of 47) breast tumor samples compared with their paired ANCTs. Transcript levels of GHET1 were shown to be associated with body mass index. No other significant association was found between the level of transcripts and patients' clinical data, such as estrogen receptor, progesterone receptor, Her2/neu status, tumor stage or grade. Conclusions: GHET1 is possibly contributed in the pathogenesis of a fraction of breast cancers

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“…Imp1 hypomorphic mice exhibit intestinal defects and perinatal lethality, yet the contribution of IMP1 to normal gut homeostasis and repair is not known (Fakhraldeen et al, 2015, Hansen et al, 2004. We utilized CRISPRmediated IMP1 deletion in the SW480 colorectal cancer cell line to evaluate "translatome"-wide effects of IMP1 loss ( Fig.…”

Section: Imp1 Knockout Reveals Global Changes In Active Translationmentioning

confidence: 99%

“…Evidence in Imp1 hypomorphic mice, which express only 20% of wild type Imp1, suggests that its expression is critical for normal growth and development, as these mice exhibit high perinatal mortality and morphological defects in intestine epithelium (Fakhraldeen et al, 2015, Hansen et al, 2004. We therefore evaluated VillinCre; Imp1 fl/fl mice (Imp1 ΔIEC mice), in which IMP1 is deleted solely in intestinal and colonic epithelium (Hamilton et al, 2013).…”

Section: Mice With Imp1 Loss Exhibit Morphological Changes In Paneth mentioning

confidence: 99%

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Posttranscriptional regulation of intestinal epithelial cell repair by RNA binding protein IMP1

Chatterji

et al. 2018

Preprint

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RNA binding proteins, such as IMP1, are emerging as essential regulators of intestinal development and cancer. IMP1 hypomorphic mice exhibit severe intestinal growth defects, yet it's role in adult intestinal epithelium is unclear. We employed ribosome profiling to test the effect of IMP1 loss on the "translatome" in colon cancer cell lines. In parallel, we evaluated mice with intestinal epithelial-specific Imp1 deletion (Imp1 ΔIEC ) following irradiation or colitis models. Ribosome-profiling revealed translation efficiency changes for multiple pathways important for intestinal homeostasis, including autophagy, in IMP1 knockout cells. We found increased autophagy flux in Imp1 ΔIEC mice, reinforced through in silico and biochemical analyses revealing direct binding of IMP1 to autophagy transcripts MAP1LC3B and ATG3. We found that Imp1 ΔIEC mice exhibit enhanced recovery following irradiation, which is attenuated with genetic deletion of autophagy gene Atg7.Finally, we demonstrated that IMP1 is upregulated in Crohn's disease patients and Imp1 loss lessened colitis severity in mice. These studies demonstrate that IMP1 acts as a posttranscriptional regulator of gut epithelial repair post-irradiation and colitis, in part through modulation of autophagy.

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Two Isoforms of the RNA Binding Protein, Coding Region Determinant-binding Protein (CRD-BP/IGF2BP1), Are Expressed in Breast Epithelium and Support Clonogenic Growth of Breast Tumor Cells

Cited by 48 publications

References 52 publications

Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon

Loss of Stromal IMP1 Promotes a Tumorigenic Microenvironment in the Colon

Long non-coding RNA GHET1 Is Possibly Involved in the Pathogenesis of a Fraction of Breast Cancers

Posttranscriptional regulation of intestinal epithelial cell repair by RNA binding protein IMP1

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