Biology Reference
In-Depth Information
EMT
Epithelial-mesenchymal transition
FCS
Fetal calf serum
LC
Liquid chromatography
MDCK
Madin Darby canine kidney
MS
Mass spectrometry
RT
Room temperature
1. Introduction
Metastasis is the leading cause of cancer-related mortality despite
advances in early detection of the disease and new therapeutic
treatments (
1
). Understanding the cellular mechanisms that
enhance tumorigenesis has been a major challenge, and to date,
the molecular details surrounding metastatic progression remain
unresolved (
2
). The current metastatic paradigm consists of several
steps, all of which are required to achieve tumor spreading (
3, 4
).
First, cancer cells breach the basement membrane, and individual
cells dissociate from the bulk of the tumor (
3, 5, 6
). Cells then
invade neighboring tissue, intravasate into blood and lymph vessels,
and transport to distant sites (
3, 5, 6
). Finally, cells lodge, and out-
grow to form micrometastases and secondary tumors (
3, 5, 6
).
The process underlying the initial breach of the basement mem-
brane and release of cancer cells from their neighbors has been
postulated by many to involve epithelial-mesenchymal transition
(EMT) (
7-9
). EMT is broadly defi ned by diminished epithelial
characteristics and increased mesenchymal attributes (
10
). These
changes encompass many diverse alterations including loss of cell
polarity, reduced cellular adhesion, and acquisition of enhanced
cell migration and invasion (
11-13
). Importantly, EMT can
promote metastasis in several ways including the loss of cell-cell
adhesion to facilitate tumor cell invasion (
14
), induce secretion of
protein degrading enzymes such as matrix metalloproteinases to
remodel the extracellular matrix (
15
), stimulate cell signaling path-
ways such as Wnt and TFG-
to increase cell motility (
16, 17
), and
induce the expression of the mesenchymal transcriptional program
to modulate the EMT process (
18, 19
).
Over the years, classical molecular and cell biology-based
approaches have helped us understand many molecular mechanisms
of EMT; however, they are usually restricted by the number of tar-
gets that can be monitored in any one experiment. Interdisciplinary
approaches such as transcriptomics and proteomics have the poten-
tial to further our understanding of complex regulation, as they are
able to expression profi le multiple targets simultaneously without
bias (
β
20, 21
). For example, numerous studies have employed tran-
script gene expression analysis to reveal new potential markers in
well-characterized EMT models (
22, 23
). While informative, it is
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