The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis.
BACKGROUND
Lung cancer is the most common cause of cancer deaths in the western world. Progress in treatment results has been limited, and the prognosis is poor with a 5-year survival less than 15%. Based on new developments in molecular biology, our knowledge about lung carcinogenesis and mechanisms for invasion and metastasis has expanded and may in the future lead to more specific targeted therapies and better prognosis. The E-cadherin-catenin complex is critical for intercellular adhesiveness and maintenance of normal and malignant tissue architecture. Reduced expression of this complex in malignant disease is associated with tumour invasion, metastasis, and unfavorable prognosis.


METHODS
This review is based on search in the Medline database from 1991 to 2001. We have reviewed the relevance of the E-cadherin-catenin adhesion complex in malignancy in general and lung cancer in particular. Furthermore, its role as target for specific therapy is discussed.


RESULTS
Available data indicate that alterations of proteins involved in the E-cadherin-catenin complex are early incidents in cancer development. Reduced or altered expression of one or more of the components in this complex is associated with extended invasive and progressive behavior of cancer cells. Consistently, the E-cadherin-catenin complex appears to be increasingly delicate with regard to cancer prognosis. beta-Catenin, one of the components of the adhesion complex, also plays a significant role in cell signal transduction, gene activation, apoptosis inhibition, and increased cellular proliferation and migration.


CONCLUSIONS
Inactivation of the E-cadherin-catenin adhesion complex, induced by genetic and epigenetic events, plays a significant role in multistage carcinogenesis, and seems to be associated with dedifferentiation, local invasion, regional metastasis, and reduced survival in lung cancer.
Bremnes
Roy M
RM
Department of Pathology, University of Colorado Cancer Center, Denver, USA. kreftrmb@rito.no
Veve
Robert
R
Hirsch
Fred R
FR
Franklin
Wilbur A
WA
D000970:Antineoplastic Agents / Q000627:therapeutic use; D015820:Cadherins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000628:therapy; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D011379:Prognosis; D015398:Signal Transduction
D000970:Antineoplastic Agents; D015820:Cadherins; D003598:Cytoskeletal Proteins