Journal
CANCER AND METASTASIS REVIEWS
Volume 24, Issue 3, Pages 413-423Publisher
SPRINGER
DOI: 10.1007/s10555-005-5133-4
Keywords
integrin; alpha 6 beta 4; carcinoma; PI3-K; survival; translation
Categories
Funding
- NATIONAL CANCER INSTITUTE [R01CA089208, R01CA080789] Funding Source: NIH RePORTER
- NCI NIH HHS [CA 80879, R01 CA080789, CA89208] Funding Source: Medline
Ask authors/readers for more resources
This review examines the hypothesis that the function of the alpha 6 beta 4 integrin is altered substantially as normal epithelia undergo malignant transformation and progress to invasive carcinoma and that the functions of this integrin contribute to the behavior of aggressive carcinoma cells. Specifically, alpha 6 beta 4 functions primarily as an adhesion receptor in normal epithelia, often as a component of hemidesmosomes and associated with intermediate filaments. Factors in the host-tumor microenvironment have the potential to mobilize alpha 6 beta 4 from hemidesmosomes and promote its association with F-actin in lamellae and filopodia, a process that is mediated by PKC-dependent phosphorylation of the beta 4 cytoplasmic domain. Importantly, this altered localization of alpha 6 beta 4 appears to be coupled to an activation of its signaling potential, which may occur through its association with growth factor receptors or lipid rafts, possibilities that are not mutually exclusive. The primal signaling event triggered by alpha 6 beta 4 appears to be activation of PI3-K and this activation has profound consequences on the migration, invasion and survival of carcinoma cells. Arguably, the ability of alpha 6 beta 4 to stimulate the PI3-K-dependent translation of VEGF and possibly other growth factors may be the most significant contribution of this integrin to carcinoma because of the potential autocrine and paracrine effects of these factors.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available