FERM domain proteins

1
FERM domain proteins
and their involvement in metastasis
Merlin and ERM proteins unappreciated roles in
cancer development? A McClatchey Nat Rev Cancer
3(11)877-83 (2003)
2
The phylogeny of the FERM domain
ERM proteins and Merlin Integrators at the cell
cortex, Bretscher A et al. 2002
3
Conformational regulation of FERM domain proteins
ERM proteins and Merlin Integrators at the cell
cortex, Bretscher A et al. 2002
4
The role of ERM
Perturbation of cell adhesion and microvilli
formation by antisense oligonucleotides to ERM
family members, K Takeuchi et al, J Cell Bio
1251371-1384(1994)
5
Ezrin and metastasis
The membrane-cytoskeleton linker ezrin is
necessary for osteosarcoma metastasis Khanna C et
al. Nature Medicine 10182-186 (2004)
Cancer Res 65(6) 2406-2411 (2005)
6
Assaying cell motility and invasion when
overexpressing wild type or dominant negative
forms of Ezrin
The membrane cytoskeletal crosslinker ezrin is
required for metastasis of breast carcinoma
cells BE Elliott et al. Breast Cancer Research
7R365-R373 (2005)
7
A dominant negative form of Merlin transforms
cells
Cellular transformation by a FERM domain mutant
of the Nf2 tumor suppressor gene Johnson KC et
al. Oncogene 21 5990-5997 (2002)
In confluent Nf2-/- cells EGFR signaling
persists. Merlin creates negative regulation of
EGFR by restraining it to a membrane compartment.
Inhibitors of EGFR arrest proliferation of
Nf2-/- cells. Contact-dependent inhibition of
EGFR signaling by Nf2/Merlin M Curto et al. J
Cell Biology 177(5) 893-903 (2007)
8
4.1B suppresses metastasis
Protein 4.1B suppresses prostate cancer
progression and metastasis SY Wong et al. PNAS
104 12784-12789 (2007)
9
4.1 family members altered in ependymomas
Alterations of protein 4.1 family members in
ependymomas a study of 84 cases V Rajaram et al.
Modern Pathology 18991-997(2005)
10
Epb4.1l5 and its role in epithelial-mesenchymal
transition during embryonic development
epiblast
mesoderm
endoderm
The FERM protein Epb4.1l5 is required for
organization of the neural plate and for the
epithelial-mesenchymal tranition at the primitive
streak of the mouse embryo JD Lee et al.
Development 134 2007-2016 (2007)
11
ERM protein interactions and implications CD44
Inhibition of human melanoma growth and
metastasis in vivo by anti-CD44 monoclonal
antibody Y Guo et al. Cancer Research
541561-1565 (1994)
12
ERM protein interactions and implications NHERF
Suppression of breast cancer cell growth by
Na/H exchanger regulatory factor 1 (NHERF1) Y
Pan et al. Breast Cancer Research 9R63-R73 (2006)
13
ERM protein interactions and implications ER?
Extra-nuclear signaling of estrogen receptor to
breast cancer cytoskeletal remodeling, migration
and invasion MS Giretti et al. PLoS ONE
3(5)e2338 (2008)
14
ERM protein interactions and implications 4.1R
and the cell cycle
Downregulation of Protein 4.1R, a mature
centriole protein, disrupts centrosomes, alters
cell cycle progression, and perturbs mittotic
spindles and anaphase SW Krauss et al. Mol and
Cell Biology 28(7)2283-2294 (2008)
15
Summary Compare and contrast in the FERM domain
proteins roles in cancer development
Merlin and ERM proteins unappreciated roles in
cancer development? A McClatchey Nat Rev Cancer
3(11)877-83 (2003)