| First Author | Joshi J | Year | 2008 |
| Journal | EMBO J | Volume | 27 |
| Issue | 16 | Pages | 2181-93 |
| PubMed ID | 18650932 | Mgi Jnum | J:139014 |
| Mgi Id | MGI:3807109 | Doi | 10.1038/emboj.2008.149 |
| Citation | Joshi J, et al. (2008) Par-4 inhibits Akt and suppresses Ras-induced lung tumorigenesis. EMBO J 27(16):2181-93 |
| abstractText | The atypical PKC-interacting protein, Par-4, inhibits cell survival and tumorigenesis in vitro, and its genetic inactivation in mice leads to reduced lifespan, enhanced benign tumour development and low-frequency carcinogenesis. Here, we demonstrate that Par-4 is highly expressed in normal lung but reduced in human lung cancer samples. We show, in a mouse model of lung tumours, that the lack of Par-4 dramatically enhances Ras-induced lung carcinoma formation in vivo, acting as a negative regulator of Akt activation. We also demonstrate in cell culture, in vivo, and in biochemical experiments that Akt regulation by Par-4 is mediated by PKCzeta, establishing a new paradigm for Akt regulation and, likely, for Ras-induced lung carcinogenesis, wherein Par-4 is a novel tumour suppressor. |
