Acquired mutations and transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences

Priedigkeit, Nolan; Ding, Kai; Horne, William; Kolls, Jay K.; Du, Tian; Lucas, Peter C.; Blohmer, Jens-Uwe; Denkert, Carsten; Machleidt, A; Ignold-Heppner, Barbara; Oesterreich, Steffi; Lee, Adrian V.

doi:10.1101/2020.06.08.140707

Cited by 4 publications

(5 citation statements)

References 75 publications

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“…This group includes several proteins that play a role in eye morphogenesis in Drosophila and humans ( Jukam and Desplan, 2011 ; Mahato et al, 2018 ; Marrone et al, 2011a ; Ray et al, 2020 ). Moreover, these factors are not only associated with various ocular dystrophies but also involved in cancer development and regulation of stem cell maintenance and differentiation, cell growth, and metabolism ( Cehajic-Kapetanovic et al, 2019 ; Collison et al, 2019 ; Jamal et al, 2020 ; Lu et al, 2019 ; Priedigkeit et al, 2021 ; Wu et al, 2020 ). For example, in Drosophila, prominin (Prom), a homolog of human CD133, maintains mitochondrial function, regulates body size and weight, and influences animal longevity by controlling insulin and TOR signaling ( Ryu et al, 2019 ; Wang et al, 2019 ; Zheng et al, 2019 ).…”

Section: Resultsmentioning

confidence: 99%

Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

Yatsenko

Kucherenko

Xie

et al. 2021

eLife

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To assemble a brain, differentiating neurons must make proper connections and establish specialized brain compartments. Abnormal levels of cell adhesion molecules disrupt these processes. Dystroglycan (Dg) is a major non-integrin cell adhesion receptor, deregulation of which is associated with dramatic neuroanatomical defects such as lissencephaly type II, or cobblestone brain. The previously established Drosophila model for cobblestone encephaly was used to understand how Dg is regulated in the brain. During development, Dg has a spatiotemporally dynamic expression pattern, fine-tuning of which is crucial for accurate brain assembly. In addition, mass spectrometry analyses identified numerous components associated with Dg in neurons, including several proteins of the exocyst complex. Data show that exocyst-based membrane trafficking of Dg allows its distinct expression pattern, essential for proper brain morphogenesis. Further studies of the Dg neuronal interactome will allow identification of new factors involved in the development of dystroglycanopathies and advance disease diagnostics in humans.

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Section: Resultsmentioning

confidence: 99%

Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

Yatsenko

Kucherenko

Xie

et al. 2021

eLife

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“…The importance of PROM1 in BRCA has been reported. Priedigkeit to transcriptional remodeling in long-term estrogendeprived locoregional breast cancer recurrences [23]. Bertheau et al identified PROM1 as a mutant TP53associated gene involved in breast cancer [24].…”

Section: Discussionmentioning

confidence: 99%

Prominin 1 Significantly Correlated with Bone Metastasis of Breast Cancer and Influenced the Patient’s Prognosis

et al. 2022

BioMed Research International

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Background. This study is aimed at identifying the important biomarkers associated with bone metastasis (BM) in breast cancer (BRCA). Methods. The GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and DEG-related pathways were then explored. Further, we constructed the protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes. We then performed the Cox regression, Kaplan-Meier analysis, nomogram, and ROC curve to filter the most significant prognosis genes. The GSE14020 and GSE124647 datasets were used to verify the expression and prognostic value of hub genes, respectively. Finally, the gene set enrichment analysis (GSEA) was performed to reveal the potential mechanism. Results. Totally, 74 DEGs were detected, which mainly correlated with infectious disease, signaling molecules, and interaction. The 5 important DEGs were then filtered, and the Cox regression further showed that 2 genes, including prominin 1 (PROM1) and C-C motif chemokine ligand 2 (CCL2), were related to the prognosis of BRCA metastasis patients. Especially, PROM1 presented a better prognostic performance on the survival probability of patients than CCL2. Verification analysis further confirmed the abnormal expression and significant prognostic influence of PROM1. Finally, GSEA revealed that PROM1 was negatively related to IGF1 and mTOR pathways in BRCA metastasis. Conclusion. PROM1 was an important biomarker associated with BRCA bone metastasis and affected the prognosis of metastatic BRCA patients. It may play a vital role in metastatic BRCA by negatively regulating IGF1 and mTOR pathways.

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“…At present, there were few kinds of research reporting the role of PROM1 in BRCA. Priedigkeit et al reported that PROM1 was related to transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences [24]. Bertheau et al identi ed PROM1 as a mutant TP53-associated gene involved in breast cancer [25].…”

Section: Discussionmentioning

confidence: 99%

Prominin-1 (PROM1) Significantly Correlated With Bone Metastasis and Influenced Prognosis in Breast Cancer

et al. 2021

Preprint

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BackgroundThis study aimed to explore the important biomarker associated with bone metastasis (BM) in breast cancer (BRCA).MethodsThe GSE175692 dataset was used to detect significant differential expressed genes (DEGs) between BRCA samples with or without BM, and important pathways were then explored. Further, we constructed protein-protein interaction (PPI) network on GEGs and filtered 5 vital nodes. Through performing cox regression, Kaplan-Meier analysis, nomogram, ROC curve, and risk score model, significant prognostic factor was gradually identified. Finally, gene set enrichment analysis (GSEA) analysis was performed to reveal the potential mechanism.ResultsTotally, 74 DEGs were detected, which mainly correlated with infectious disease, signaling molecules and interaction. The 5 important DEGs were filtered, and cox regression further showed that prominin-1 (PROM1) and C-C Motif Chemokine Ligand 2 (CCL2) were prognosis-related factors. A negative correlation was observed between the expression of these 2 genes and the overall survival of metastatic BRCA patients. Especially, PROM1 presented a better prognostic performance on the survival probability of patients. Prognosis verification analysis also confirmed the significant influence of PROM1 on patient’s survival. In addition, we found that PROM1 expression was related to the distant metastasis-free survival in BRCA. Finally, GSEA analysis revealed that PROM1 was negatively related to IGF1 and mTOR pathways involved in BRCA metastasis. ConclusionPROM1 was identified as an important DEGs associated with BRCA bone metastasis. It acted as a vital prognostic biomarker involved in BRCA metastasis, which may be due to the negative regulation of IGF1 and mTOR pathways.

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Acquired mutations and transcriptional remodeling in long-term estrogen-deprived locoregional breast cancer recurrences

Cited by 4 publications

References 75 publications

Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

Exocyst-mediated membrane trafficking of the lissencephaly-associated ECM receptor dystroglycan is required for proper brain compartmentalization

Prominin 1 Significantly Correlated with Bone Metastasis of Breast Cancer and Influenced the Patient’s Prognosis

Prominin-1 (PROM1) Significantly Correlated With Bone Metastasis and Influenced Prognosis in Breast Cancer

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