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Pan-cancer analysis reveals TAp63-regulated oncogenic lncRNAs that promote cancer progression through AKT activation.

Abstract：

:The most frequent genetic alterations across multiple human cancers are mutations in TP53 and the activation of the PI3K/AKT pathway, two events crucial for cancer progression. Mutations in TP53 lead to the inhibition of the tumour and metastasis suppressor TAp63, a p53 family member. By performing a mouse-human cross species analysis between the TAp63 metastatic mammary adenocarcinoma mouse model and models of human breast cancer progression, we identified two TAp63-regulated oncogenic lncRNAs, TROLL-2 and TROLL-3. Further, using a pan-cancer analysis of human cancers and multiple mouse models of tumour progression, we revealed that these two lncRNAs induce the activation of AKT to promote cancer progression by regulating the nuclear to cytoplasmic translocation of their effector, WDR26, via the shuttling protein NOLC1. Our data provide preclinical rationale for the implementation of these lncRNAs and WDR26 as therapeutic targets for the treatment of human tumours dependent upon mutant TP53 and/or the PI3K/AKT pathway.

journal_name

Nat Commun

journal_title

Nature communications

authors

Napoli M,Li X,Ackerman HD,Deshpande AA,Barannikov I,Pisegna MA,Bedrosian I,Mitsch J,Quinlan P,Thompson A,Rajapakshe K,Coarfa C,Gunaratne PH,Marchion DC,Magliocco AM,Tsai KY,Flores ER

doi

10.1038/s41467-020-18973-w

subject

Has Abstract

pub_date

2020-10-14 00:00:00

pages

5156

issue

1

issn

2041-1723

pii

10.1038/s41467-020-18973-w

journal_volume

11

pub_type

杂志文章

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