Autocrine signaling in carcinoma: VEGF and the alpha6beta4 integrin.
This review highlights an emerging function for vascular endothelial growth factor (VEGF) in carcinoma and discusses mechanisms involved in the elaboration of VEGF autocrine loops. Evidence is provided that autocrine VEGF contributes to the two major components of invasive carcinoma: survival and migration. Moreover, the findings discussed support the hypothesis that carcinoma progression selects for cells that depend on VEGF as a survival factor. Furthermore, a related hypothesis, which is developed, is that the function of the alpha6beta4 integrin, which has been implicated in carcinoma progression, is linked to its ability to regulate VEGF translation and, consequently, autocrine VEGF signaling. The findings reviewed challenge the notion that the function of VEGF in cancer is limited to angiogenesis and suggest that VEGF and VEGF receptor-based therapeutics, in addition to targeting angiogenesis, may also impair tumor cell survival and invasion directly.
Mercurio
Arthur M
AM
Division of Cancer Biology and Angiogenesis, Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA. amercuri@bidmc.harvard.edu
Bachelder
Robin E
RE
Bates
Richard C
RC
Chung
Jun
J
D019898:Autocrine Communication; D002277:Carcinoma / Q000378:metabolism*; D006801:Humans; D039161:Integrin alpha6beta4 / Q000378:metabolism*; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology*
D039161:Integrin alpha6beta4; D042461:Vascular Endothelial Growth Factor A