| First Author | Mangialardi EM | Year | 2019 |
| Journal | Oncotarget | Volume | 10 |
| Issue | 59 | Pages | 6378-6390 |
| PubMed ID | 31695845 | Mgi Jnum | J:316265 |
| Mgi Id | MGI:6831644 | Doi | 10.18632/oncotarget.27293 |
| Citation | Mangialardi EM, et al. (2019) Investigating the duality of Inpp4b function in the cellular transformation of mouse fibroblasts. Oncotarget 10(59):6378-6390 |
| abstractText | Inositol Polyphosphate 4-Phosphatase, Type II (INPP4B) is a tumour suppressor in breast, ovarian, prostate, thyroid and other cancers, attributed to its ability to reduce oncogenic Akt-signaling. However, emerging studies show that INPP4B also has tumour-promoting properties in cancers including acute myeloid leukemia, colon cancer, melanoma and breast cancer. Together these findings suggest that INPP4B may be a context dependent cancer gene. Whether INPP4B functions solely in a tumour suppressing or tumour promoting manner, or both in non-transformed cells is currently not clear. In this study, consequences of deficiency and overexpression of INPP4B on cellular transformation was investigated using a mouse embryonic fibroblast (MEF) model of cellular transformation. We observed that neither deficiency nor overexpression of INPP4B was sufficient to induce neoplastic transformation, alone or in combination with H-Ras (V12) or E1A overexpression. However, Inpp4b-deficiency did cooperate with SV40 T-Large-mediated cellular transformation, a finding which was associated with increased phosphorylated-Akt levels. Transformation and phosphorylated-Akt levels were dampened upon overexpression of INPP4B in SV40 T-Large-MEF. Together, our findings support a model where INPP4B function suppresses transformation mediated by SV40 T-Large, but is inconsequential for Ras and E1A mediated transformation. |
