Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition

Flores Naselli, Laura Saieva, Riccardo Alessandro, Giovanni Zito, Stefania Raimondo, Stefano Forte, Rosalba Parenti, Giovanna Calabrese, Christian Rolfo, Christian Diego Rolfo

Risultato della ricerca: Article

7 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)4770-
Numero di pagine14
RivistaDefault journal
Volume7
Stato di pubblicazionePublished - 2017

Fingerprint

Tretinoin
Non-Small Cell Lung Carcinoma
Protein-Tyrosine Kinases
Growth
Pharmacology
G1 Phase Cell Cycle Checkpoints
Neoplasms
Acute Promyelocytic Leukemia
Hematologic Diseases
Therapeutics
Lung Neoplasms
Transcription Factors
Adenocarcinoma of lung
Lung
Research

All Science Journal Classification (ASJC) codes

  • General

Cita questo

Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition. / Naselli, Flores; Saieva, Laura; Alessandro, Riccardo; Zito, Giovanni; Raimondo, Stefania; Forte, Stefano; Parenti, Rosalba; Calabrese, Giovanna; Rolfo, Christian; Rolfo, Christian Diego.

In: Default journal, Vol. 7, 2017, pag. 4770-.

Risultato della ricerca: Article

@article{cde0bbafb07244e482f5b424ae109017,
title = "Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition",
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.",
author = "Flores Naselli and Laura Saieva and Riccardo Alessandro and Giovanni Zito and Stefania Raimondo and Stefano Forte and Rosalba Parenti and Giovanna Calabrese and Christian Rolfo and Rolfo, {Christian Diego}",
year = "2017",
language = "English",
volume = "7",
pages = "4770--",
journal = "Default journal",

}

TY - JOUR

T1 - Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition

AU - Naselli, Flores

AU - Saieva, Laura

AU - Alessandro, Riccardo

AU - Zito, Giovanni

AU - Raimondo, Stefania

AU - Forte, Stefano

AU - Parenti, Rosalba

AU - Calabrese, Giovanna

AU - Rolfo, Christian

AU - Rolfo, Christian Diego

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

UR - http://hdl.handle.net/10447/238060

M3 - Article

VL - 7

SP - 4770-

JO - Default journal

JF - Default journal

ER -