Publication
Title
Retinoic zcid affects lung adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition
Author
Abstract
A fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved in the physiological differentiation of the distal lung. In addition, our results demonstrate that RA inhibits EGFR and Wnt signaling activation, two pathways involved in NSCLC progression. Furthermore, we uncovered a novel mechanism in NSCLC that shows how RA exerts its function; we found that RA-mediated GATA6 activation is necessary for EGFR and Wnt inhibition, thus leading to 1) increased differentiation and 2) loss of proliferation. All together, these findings prove that differentiation therapy might be feasible in TKI resistant NSCLCs, and shed light on new targets to define new pharmacological therapies.
Language
English
Source (journal)
Scientific reports. - London, 2011, currens
Publication
London : Nature Publishing Group , 2017
ISSN
2045-2322
Volume/pages
7 (2017) , 14 p.
Article Reference
4770
ISI
000404841100026
Medium
E-only publicatie
Full text (Publisher's DOI)
Full text (open access)
UAntwerpen
Faculty/Department
Research group
Publication type
Subject
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 02.08.2018
Last edited 20.09.2021
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