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 metastasisKhanna 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 cellsBE 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 geneJohnson 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/MerlinM Curto et al. J Cell Biology 177(5): 893-903 (2007)

4.1B suppresses metastasis

Protein 4.1B suppresses prostate cancer progression and metastasisSY 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 casesV Rajaram et al. Modern Pathology 18:991-997(2005)

Epb4.1l5 and its role in epithelial-mesenchymal transition during embryonic development

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 embryoJD Lee et al. Development 134: 2007-2016 (2007)

epiblast

mesodermendoderm

ERM protein interactions and implications: CD44

Inhibition of human melanoma growth and metastasis in vivo by anti-CD44 monoclonal antibodyY 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 invasionMS 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

SW Krauss et al. Mol and Cell Biology 28(7):2283-2294 (2008)

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)