TRIB3 confers radiotherapy resistance in esophageal squamous cell carcinoma by stabilizing TAZ.

Abstract:

:Radioresistance becomes the major obstacle to reduce tumor recurrence and improve prognosis in the treatment of esophageal squamous cell carcinoma (ESCC). Thus new strategies for radioresistant ESCC are urgently needed. Herein, we reported that tribbles pseudokinase 3 (TRIB3) serves as a key regulator of radioresistance in ESCC. TRIB3 is overexpressed in ESCC tissues and cell lines. High expression of TRIB3 significantly correlates with poor radiotherapy response and prognosis in ESCC patients. Upregulation of TRIB3 in ESCC cells conferred radioresistance in vitro and in vivo by interacting with TAZ thus impeding β-TrCP-mediated TAZ ubiquitination and degradation. Conversely, silencing TRIB3 sensitized ESCC cells to ionizing radiation. More importantly, TRIB3 was significantly correlated with TAZ activation in ESCC biopsies, and patients with high expression of both TRIB3 and TAZ suffered the worst radiotherapy response and survival. Our study uncovers the critical mechanism of ESCC resistance to radiotherapy, and provides a new pharmacological opportunity for developing a mechanism-based strategy to eliminate radioresistant ESCC in clinical practice.

journal_name

Oncogene

journal_title

Oncogene

authors

Zhou S,Liu S,Lin C,Li Y,Ye L,Wu X,Jian Y,Dai Y,Ouyang Y,Zhao L,Liu M,Song L,Xi M

doi

10.1038/s41388-020-1245-0

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

3710-3725

issue

18

eissn

0950-9232

issn

1476-5594

pii

10.1038/s41388-020-1245-0

journal_volume

39

pub_type

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