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Haploinsufficiency of the ESCRT Component HD-PTP Predisposes to Cancer.

Abstract：

: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 β1-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.

journal_name

Cell Rep

journal_title

Cell reports

authors

Manteghi S,Gingras MC,Kharitidi D,Galarneau L,Marques M,Yan M,Cencic R,Robert F,Paquet M,Witcher M,Pelletier J,Pause A

doi

10.1016/j.celrep.2016.04.076

subject

Has Abstract

pub_date

2016-05-31 00:00:00

pages

1893-900

issue

9

issn

2211-1247

pii

S2211-1247(16)30520-4

journal_volume

15

pub_type

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