The role of genes co-amplified with nicastrin in breast invasive carcinoma

Sarajlić, Anida; Filipović, Aleksandra; Janjić, Vuk; Coombes, R. Charles; Pržulj, Nataša

doi:10.1007/s10549-013-2805-6

Cited by 6 publications

(6 citation statements)

References 44 publications

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“…5B ). When we looked at genes potentially co-amplified with PBX1 (chr1q23.3) [ 27 ] we found that very few candidates were also over-expressed in breast cancer ( Fig. S10A ).…”

Section: Resultsmentioning

confidence: 99%

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

et al. 2015

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Over 30% of ERα breast cancer patients develop relapses and progress to metastatic disease despite treatment with endocrine therapies. The pioneer factor PBX1 translates epigenetic cues and mediates estrogen induced ERα binding. Here we demonstrate that PBX1 plays a central role in regulating the ERα transcriptional response to epidermal growth factor (EGF) signaling. PBX1 regulates a subset of EGF-ERα genes highly expressed in aggressive breast tumours. Retrospective stratification of luminal patients using PBX1 protein levels in primary cancer further demonstrates that elevated PBX1 protein levels correlate with earlier metastatic progression. In agreement, PBX1 protein levels are significantly upregulated during metastatic progression in ERα-positive breast cancer patients. Finally we reveal that PBX1 upregulation in aggressive tumours is partly mediated by genomic amplification of the PBX1 locus. Correspondingly, ERα-positive breast cancer patients carrying PBX1 amplification are characterized by poor survival. Notably, we demonstrate that PBX1 amplification can be identified in tumor derived-circulating free DNA of ERα-positive metastatic patients. Metastatic patients with PBX1 amplification are also characterized by shorter relapse-free survival. Our data identifies PBX1 amplification as a functional hallmark of aggressive ERα-positive breast cancers. Mechanistically, PBX1 amplification impinges on several critical pathways associated with aggressive ERα-positive breast cancer.

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“…5B ). When we looked at genes potentially co-amplified with PBX1 (chr1q23.3) [ 27 ] we found that very few candidates were also over-expressed in breast cancer ( Fig. S10A ).…”

Section: Resultsmentioning

confidence: 99%

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

et al. 2015

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“…Our results revealed that the cellular status of AKT1 might determine the magnitude of splice variance ( Figure 6 ). Interestingly, many of the examples of the top 10 highly dispersed splicing events affected by the status of AKT1 have been previously implicated in cancerous phenotypes [ 63 , 68 , 69 , 70 , 71 , 72 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 ]. Though not in the top 10, we also found examples of AKT1-dependent transcripts that also underwent differential splicing in a manner dependent on the presence or silencing of AKT1.…”

Section: Discussionmentioning

confidence: 99%

AKT1 Transcriptomic Landscape in Breast Cancer Cells

George

Gui

Raguraman

et al. 2022

Cells

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Overexpression and hyperactivation of the serine/threonine protein kinase B (AKT) pathway is one of the most common cellular events in breast cancer progression. However, the nature of AKT1-specific genome-wide transcriptomic alterations in breast cancer cells and breast cancer remains unknown to this point. Here, we delineate the impact of selective AKT1 knock down using gene-specific siRNAs or inhibiting the AKT activity with a pan-AKT inhibitor VIII on the nature of transcriptomic changes in breast cancer cells using the genome-wide RNA-sequencing analysis. We found that changes in the cellular levels of AKT1 lead to changes in the levels of a set of differentially expressed genes and, in turn, imply resulting AKT1 cellular functions. In addition to an expected positive relationship between the status of AKT1 and co-expressed cellular genes, our study unexpectedly discovered an inherent role of AKT1 in inhibiting the expression of a subset of genes in both unstimulated and growth factor stimulated breast cancer cells. We found that depletion of AKT1 leads to upregulation of a subset of genes—many of which are also found to be downregulated in breast tumors with elevated high AKT1 as well as upregulated in breast tumors with no detectable AKT expression. Representative experimental validation studies in two breast cancer cell lines showed a reasonable concurrence between the expression data from the RNA-sequencing and qRT-PCR or data from ex vivo inhibition of AKT1 activity in cancer patient-derived cells. In brief, findings presented here provide a resource for further understanding of AKT1-dependent modulation of gene expression in breast cancer cells and broaden the scope and significance of AKT1 targets and their functions.

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“…These membrane proteins have not been reported in previous cervical cancer studies; however, published reports support their involvement in other cancer types, as shown in Table III. Nicastrin in particular is considered as a putative therapeutic target in breast cancer (25,26), and further investigation of its potential for cervical cancer therapy is warranted. Thus, the identified membrane proteins reveal novel perspectives for the molecular characterization of cervical cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The most prominent differentially expressed proteins (TMX2, FAM120A, CLPTM1, CKAP5 and NCSTN) that followed the same pattern of expression in all cancer cell lines are presented in Table III, along with information on their molecular function. Moreover, for these specific proteins, a literature search was performed on previous relevant studies describing their role in cancer biology (20)(21)(22)(23)(24)(25)(26), which was incorporated in Table III. IPA and PPI network. To further characterize the biological functions and pathways relevant to the differentially expressed proteins, IPA software was employed.…”

Section: Analysis Of Protein Differential Expression In the Siha Helamentioning

confidence: 99%

Membrane proteomics of cervical cancer cell lines reveal insights on the process of cervical carcinogenesis

et al. 2018

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The available therapeutic approaches for cervical cancer can seriously affect the fertility potential of patient; thus, there is a pressing requirement for less toxic and targeted therapies. The membrane proteome is a potential source of therapeutic targets; however, despite the significance of membrane proteins in cancer, proteomic analysis has been a challenging task due to their unique biochemical properties. The aim of the present study was to develop an efficient membrane protein enrichment protocol, and to the best of our knowledge, to compare for the first time the expression pattern of membrane proteins of one normal cell line, HCK1T, and three cervical cancer cell lines, C33A, a human papilloma virus (HPV)-negative cell line, and two HPV-positive cell lines, SiHa (HPV16+) and HeLa (HPV18+). The study aimed to identify the proteins that are involved in cervical carcinogenesis and may constitute novel drug targets. Membrane protein isolation, liquid chromatography coupled with tandem mass spectrometry proteomics and bioinformatics analysis were performed in the membrane fraction of the informative cervical cell lines following a novel enrichment protocol. The percentages of membrane and transmembrane proteins in the enrichment protocol were higher compared with those of the corresponding data derived from total cell extract analysis. Differentially expressed proteins were detected by the comparison of the cervical cancer cell lines with the normal cell line. These proteins constitute molecular features of cancer pathology and participate in biological pathways relevant to malignancy, including 'HIPPO signaling', 'PI3K/Akt signaling', 'cell cycle: G2/M DNA damage checkpoint regulation' and 'EIF2 signaling'. These unique membrane protein identifications offer insights on a previously inaccessible region of the cervical cancer proteome, and may represent putative diagnostic and prognostic markers, and eventually therapeutic targets.

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The role of genes co-amplified with nicastrin in breast invasive carcinoma

Cited by 6 publications

References 44 publications

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

The pioneer factor PBX1 is a novel driver of metastatic progression in ERα-positive breast cancer

AKT1 Transcriptomic Landscape in Breast Cancer Cells

Membrane proteomics of cervical cancer cell lines reveal insights on the process of cervical carcinogenesis

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