| First Author | Robertson CL | Year | 2014 |
| Journal | Cancer Res | Volume | 74 |
| Issue | 21 | Pages | 6184-93 |
| PubMed ID | 25193383 | Mgi Jnum | J:216688 |
| Mgi Id | MGI:5609218 | Doi | 10.1158/0008-5472.CAN-14-1357 |
| Citation | Robertson CL, et al. (2014) Genetic deletion of AEG-1 prevents hepatocarcinogenesis. Cancer Res 74(21):6184-93 |
| abstractText | Activation of the oncogene AEG-1 (MTDH, LYRIC) has been implicated recently in the development of hepatocellular carcinoma (HCC). In mice, HCC can be initiated by exposure to the carcinogen DEN, which has been shown to rely upon activation of NF-kappaB in liver macrophages. Because AEG-1 is an essential component of NF-kappaB activation, we interrogated the susceptibility of mice lacking the AEG-1 gene to DEN-induced hepatocarcinogenesis. AEG-1-deficient mice displayed resistance to DEN-induced HCC and lung metastasis. No difference was observed in the response to growth factor signaling or activation of AKT, ERK, and beta-catenin, compared with wild-type control animals. However, AEG-1-deficient hepatocytes and macrophages exhibited a relative defect in NF-kappaB activation. Mechanistic investigations showed that IL6 production and STAT3 activation, two key mediators of HCC development, were also deficient along with other biologic and epigenetics findings in the tumor microenvironment, confirming that AEG-1 supports an NF-kappaB-mediated inflammatory state that drives HCC development. Overall, our findings offer in vivo proofs that AEG-1 is essential for NF-kappaB activation and hepatocarcinogenesis, and they reveal new roles for AEG-1 in shaping the tumor microenvironment for HCC development. |
