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dc.contributor.author
Maglietta, Rosalia
dc.contributor.author
Liuzzi, Vania Cosma
dc.contributor.author
Cattaneo, Elisa
dc.contributor.author
Laczko, Endre
dc.contributor.author
Piepoli, Ada
dc.contributor.author
Panza, Anna
dc.contributor.author
Carella, Massimo
dc.contributor.author
Palumbo, Orazio
dc.contributor.author
Staiano, Teresa
dc.contributor.author
Buffoli, Federico
dc.contributor.author
Andriulli, Angelo
dc.contributor.author
Marra, Giancarlo
dc.contributor.author
Ancona, Nicola
dc.date.accessioned
2019-06-05T14:57:08Z
dc.date.available
2017-06-10T12:58:37Z
dc.date.available
2019-06-05T14:57:08Z
dc.date.issued
2012-12-19
dc.identifier.issn
1471-2407
dc.identifier.other
10.1186/1471-2407-12-608
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/62150
dc.identifier.doi
10.3929/ethz-b-000062150
dc.description.abstract
Background The malignant transformation of precancerous colorectal lesions involves progressive alterations at both the molecular and morphologic levels, the latter consisting of increases in size and in the degree of cellular atypia. Analyzing preinvasive tumors of different sizes can therefore shed light on the sequence of these alterations. Methods We used a molecular pathway-based approach to analyze transcriptomic profiles of 59 colorectal tumors representing early and late preinvasive stages and the invasive stage of tumorigenesis. Random set analysis was used to identify biological pathways enriched for genes differentially regulated in tumors (compared with 59 samples of normal mucosa). Results Of the 880 canonical pathways we investigated, 112 displayed significant tumor-related upregulation or downregulation at one or more stages of tumorigenesis. This allowed us to distinguish between pathways whose dysregulation is probably necessary throughout tumorigenesis and those whose involvement specifically drives progression from one stage to the next. We were also able to pinpoint specific changes within each gene set that seem to play key roles at each transition. The early preinvasive stage was characterized by cell-cycle checkpoint activation triggered by DNA replication stress and dramatic downregulation of basic transmembrane signaling processes that maintain epithelial/stromal homeostasis in the normal mucosa. In late preinvasive lesions, there was also downregulation of signal transduction pathways (e.g., those mediated by G proteins and nuclear hormone receptors) involved in cell differentiation and upregulation of pathways governing nuclear envelope dynamics and the G2>M transition in the cell cycle. The main features of the invasive stage were activation of the G1>S transition in the cell cycle, upregulated expression of tumor-promoting microenvironmental factors, and profound dysregulation of metabolic pathways (e.g., increased aerobic glycolysis, downregulation of pathways that metabolize drugs and xenobiotics). Conclusions Our analysis revealed specific pathways whose dysregulation might play a role in each transition of the transformation process. This is the first study in which such an approach has been used to gain further insights into colorectal tumorigenesis. Therefore, these data provide a launchpad for further exploration of the molecular characterization of colorectal tumorigenesis using systems biology approaches.
en_US
dc.format
application/pdf
en_US
dc.language.iso
en
en_US
dc.publisher
BioMed Central
en_US
dc.rights.uri
http://creativecommons.org/licenses/by/2.0/
dc.subject
Colorectal adenoma
en_US
dc.subject
Colorectal cancer
en_US
dc.subject
Transcriptomics
en_US
dc.subject
Molecular pathways
en_US
dc.subject
Cell cycle pathways
en_US
dc.subject
Random set method
en_US
dc.title
Molecular pathways undergoing dramatic transcriptomic changes during tumor development in the human colon
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution 2.0 Generic
ethz.journal.title
BMC Cancer
ethz.journal.volume
12
en_US
ethz.journal.issue
1
en_US
ethz.journal.abbreviated
BMC cancer (Online)
ethz.pages.start
608
en_US
ethz.size
16 p.
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.nebis
004406129
ethz.publication.place
London
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00003 - Schulleitung und Dienste::00022 - Bereich VP Forschung & Wirtschaftsbez. / Domain VP Research & Corporate Relations::02207 - Functional Genomics Center Zürich / Functional Genomics Center Zürich
ethz.date.deposited
2017-06-10T13:01:02Z
ethz.source
ECIT
ethz.identifier.importid
imp593650403bb7848028
ethz.ecitpid
pub:98811
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-20T17:00:19Z
ethz.rosetta.lastUpdated
2019-06-05T14:57:18Z
ethz.rosetta.versionExported
true
ethz.COinS
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