Transcript FERM domain proteins

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)
The phylogeny of the FERM domain
ERM proteins and Merlin: Integrators at the cell cortex, Bretscher A et al. 2002
Conformational regulation of FERM domain proteins
ERM proteins and Merlin: Integrators at the cell cortex, Bretscher A et al. 2002
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 125:1371-1384(1994)
Ezrin and metastasis
The membrane-cytoskeleton linker ezrin is necessary for osteosarcoma metastasis
Khanna C et al. Nature Medicine 10:182-186 (2004)
Cancer Res 65(6): 2406-2411 (2005)
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 7:R365-R373 (2005)
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)
4.1B suppresses metastasis
Protein 4.1B suppresses prostate cancer progression and metastasis
SY Wong et al. PNAS 104: 12784-12789 (2007)
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 18:991-997(2005)
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)
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 54:1561-1565 (1994)
ERM protein interactions and implications: NHERF
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Suppression of breast cancer cell growth by Na+/H+ exchanger regulatory factor 1 (NHERF1)
Y Pan et al. Breast Cancer Research 9:R63-R73 (2006)
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)
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
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)