Mutation of TGFβ-RII Eliminates NSAID Cancer Chemoprevention

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Mar 22

PMID 29560090

Citations 8

Authors

Juana Martin-Lopez

Pierluigi Gasparini

Kevin Coombes

Carlo M Croce

Gregory P Boivin

Richard Fishel

Affiliations

Soon will be listed here.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) exhibit anti-neoplastic (chemoprevention) activity for sporadic cancers and the hereditary cancer predisposition Lynch syndrome (LS/HNPCC). However, the mechanism of NSAID tumor suppression has remained enigmatic. Defects in the core mismatch repair (MMR) genes and are the principal drivers of LS/HNPCC. Previous work has demonstrated that the - (VpC-Msh2) mouse is a reliable model for LS/HNPCC intestinal tumorigenesis, which is significantly suppressed by treatment with the NSAID aspirin (ASA) similar to human chemoprevention. Here we show that including a TGFβ receptor type-II () mutation in the mouse (-- ) completely eliminates NSAID tumor suppression. These results provide strong genetic evidence that TGFβ signaling and/or effectors participate in NSAID-dependent anti-neoplastic processes and provide fresh avenues for understanding NSAID chemoprevention and resistance.

Citing Articles

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