| First Author | Manteghi S | Year | 2016 |
| Journal | Cell Rep | Volume | 15 |
| Issue | 9 | Pages | 1893-900 |
| PubMed ID | 27210750 | Mgi Jnum | J:234850 |
| Mgi Id | MGI:5791009 | Doi | 10.1016/j.celrep.2016.04.076 |
| Citation | Manteghi S, et al. (2016) Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer. Cell Rep 15(9):1893-900 |
| abstractText | Endosomal sorting complexes required for transport (ESCRT) drive cell surface receptor degradation resulting in attenuation of oncogenic signaling and pointing to a tumor suppressor function. Here, we show that loss of function of an ESCRT protein (HD-PTP encoded by the PTPN23 gene, located on the tumor suppressor gene cluster 3p21.3) drives tumorigenesis in vivo. Indeed, Ptpn23(+/-) loss predisposes mice to sporadic lung adenoma, B cell lymphoma, and promotes Myc-driven lymphoma onset, dissemination, and aggressiveness. Ptpn23(+/-)-derived tumors exhibit an unaltered remaining allele and maintain 50% of HD-PTP expression. Consistent with the role of HD-PTP in attenuation of integrin recycling, cell migration, and invasion, hemizygous Ptpn23(+/-) loss increases integrin beta1-dependent B cell lymphoma survival and dissemination. Finally, we reveal frequent PTPN23 deletion and downregulation in human tumors that correlates with poor survival. Altogether, we establish HD-PTP/PTPN23 as a prominent haploinsufficient tumor suppressor gene preventing tumor progression through control of integrin trafficking. |
