Download Research Article Summary BIOL 501-Senior Project Eboni Stafford

Research Article Summary
BIOL 501-Senior Project
Author, Title, Journal,
Year, Volume, Pages
Eboni Stafford
Tuomi, S., Mai, A., Nevo, J., Laine, J., Vilkki, V., Ohman, T., Gahmberg, C., Parker, P., Ivaska, J. (2009). PKC ε
Regulation of an α5 Integrin-ZO-1 Complex Controls Lamellae Formation in Migrating Cancer Cells . Cell
Biology. Volume 2. 77.
Key Terms
Introduction/
Purpose
Integrin, ZO-1, migrating cells
Research
Methods
Question/Hypothesis
During carcinogenesis,
epithelia cells lose their
characteristic epithelial
feature and become
increasingly motile and
invasive. Reduced ZO-1,
a tight junction protein,
has been reported to
correlate w/increased
invasiveness. Loss of
ZO-1 from intercellular
adhesions, increased
α5β1 integrin, and
activation of PKCε have
been shown to correlate
/increased invasion and
poor prognosis in lung
cancer. They want to
show that a spatially
restricted α5 integrinZO-1 interaction, which
is dynamically regulated
by PKCε, triggers
They want to show that a
spatially restricted α5
integrin- ZO-1 interaction,
which is dynamically
regulated by PKCε,
triggers persistent
migration in lung cancer
cells.
Cell culture: NCIH460 non-small cell
lung cancer cells,
immunofluorescenc
e, DNA constructs
and transfection,
PKC kinase assay,
gene silencing and
rescue,
immunohistochemis
try, ELISA,
migration assays
and cell
proliferation
analysis, adhesion
assays, inverted 3-D
invasion assay, Rac
activation assay,
Integrin
internalization
assay, Flow
cytometry,
statistical analysis
Results
Conclusion/Discussion
-ZO-1 and α5 regulate
lamelle formation and
migration
-α5β1 integrin and ZO-1
association is spatially
restricted to lamellae
-ZO-1 interacts directly
w/a noncanonical PDZ
binding motif unique to
the α5 integrin
cytoplasmic tail.
-The α5-ZO-1 complex
is present in lung cancer
clinical samples
-PKCε regulates the
formation of the α5-ZO1 complex
-Phosphorylation
regulates ZO-1
subcellular localization
Conclusion: PKCε Regulation of
an α5 Integrn-ZO- 1 complex
controls lamellae formation in
migrating cancer cells
Discussion: Transition from normal
cells to invasive cancer cells
involves disassembly of cell-cell
adhesions and remodeling of the
actin cytoskeleton and integrincontaining adhesion sites. The
migration switch is controlled by
PKCε which regulates ZO-1
phosphorylation on Ser 168. ZO-1
PDZ domains appear to have a dual
role in cells. The PKCε-regulated
localization of the α integrin-ZO-1
complex to the leading edge is a
molecular migration switch w/a
potentially critical role in cancer
cell invasion.
Research Article Summary
BIOL 501-Senior Project
persistent migration in
lung cancer cells.
Eboni Stafford