| First Author | Jinushi M | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 21 | Pages | 8889-98 |
| PubMed ID | 18974133 | Mgi Jnum | J:140637 |
| Mgi Id | MGI:3814252 | Doi | 10.1158/0008-5472.CAN-08-2147 |
| Citation | Jinushi M, et al. (2008) Milk fat globule EGF-8 promotes melanoma progression through coordinated Akt and twist signaling in the tumor microenvironment. Cancer Res 68(21):8889-98 |
| abstractText | The pathogenesis of malignant melanoma involves the interplay of tumor cells with normal host elements, but the underlying mechanisms are incompletely understood. Here, we show that milk fat globule EGF-8 (MFG-E8), a secreted protein expressed at high levels in the vertical growth phase of melanoma, promotes disease progression through coordinated alpha(v)beta(3) integrin signaling in the tumor microenvironment. In a murine model of melanoma, MFG-E8 enhanced tumorigenicity and metastatic capacity through Akt-dependent and Twist-dependent pathways. MFG-E8 augmented melanoma cell resistance to apoptosis, triggered an epithelial-to-mesenchymal transition (EMT), and stimulated invasion and immune suppression. In human melanoma cells, MFG-E8 knockdown attenuated Akt and Twist signaling and thereby compromised tumor cell survival, EMT, and invasive ability. MFG-E8-deficient human melanoma cells also showed increased sensitivity to small molecule inhibitors of insulin-like growth factor I receptor and c-Met. Together, these findings delineate pleiotropic roles for MFG-E8 in the tumor microenvironment and raise the possibility that systemic MFG-E8 blockade might prove therapeutic for melanoma patients. |
