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CMV-induced pathology: pathway and gene-gene interaction analysis.

Abstract：

:Mucoepidermoid carcinoma (MEC) is the most prevalent malignant tumor in major and minor salivary glands (SGs). We have recently identified human cytomegalovirus (hCMV) as a principle component in the multifactorial causation of SG-MEC. This finding is corroborated by the ability of the purified mouse CMV (mCMV) to induce malignant transformation of SG cells in a three-dimensional in vitro mouse model, using a similar oncogenic signaling pathway. Our prior studies indicate that the core tumor microenvironment (TME) is a key regulator of pathologic progression, particularly the cancer-associated fibroblast (CAF) component. Studies of early CAFs immunodetect aberrant expression of ECM components, as well as multiple growth factors, cytokines and transcription factors. Here we present the mechanistic insight derived from a mathematical structure ("wiring diagram") used to model complex relationships between a highly relevant (p=9.43×10(-12)) global "cancer network" of 32 genes and their known links. Detailed characterization of the functional architecture of the examined "cancer network" exposes the critical crosstalk and compensatory pathways that limit the efficacy of targeted anti-kinase therapies.

journal_name

Exp Mol Pathol

journal_title

Experimental and molecular pathology

authors

Melnick M,Deluca KA,Jaskoll T

doi

10.1016/j.yexmp.2014.06.011

subject

Has Abstract

pub_date

2014-08-01 00:00:00

pages

154-65

issue

1

eissn

0014-4800

issn

1096-0945

pii

S0014-4800(14)00095-1

journal_volume

97

pub_type

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