Oncotarget

Research Papers:

Investigating the duality of Inpp4b function in the cellular transformation of mouse fibroblasts

Emily Marie Mangialardi, Keyue Chen, Brittany Salmon, Jean Vacher and Leonardo Salmena _

PDF  |  Full Text  |  How to cite  |  Order a Reprint

Oncotarget. 2019; 10:6378-6390. https://doi.org/10.18632/oncotarget.27293

Metrics: PDF 677 views  |   Full Text 889 views  |   ?  


Abstract

Emily Marie Mangialardi1, Keyue Chen1, Brittany Salmon1, Jean Vacher2 and Leonardo Salmena1,3

1 Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada

2 Institut de Recherches Cliniques de Montréal, Département de Médecine, Université de Montréal, Montréal, Québec, Canada

3 Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada

Correspondence to:

Leonardo Salmena,email: leonardo.salmena@utoronto.ca

Keywords: Inpp4b; MEF; RAS; E1A; SV40-T-Large

Received: March 22, 2019     Accepted: October 19, 2019     Published: October 29, 2019

ABSTRACT

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-RasV12 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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 27293