Open AccessFGFR1 Oncogenic Activation Reveals an Alternative Cell of Origin of SCLC in Rb1/p53 Mice
Author(s) -
Giustina Ferone,
JiYing Song,
Oscar Krijgsman,
Jan van der Vliet,
Miranda Cozijnsen,
Ekaterina A. Semenova,
David J. Adams,
Daniel S. Peeper,
Anton Berns
Publication year - 2020
Publication title -
cell reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.264
H-Index - 154
eISSN - 2639-1856
pISSN - 2211-1247
DOI - 10.1016/j.celrep.2020.02.052
Subject(s) - context (archaeology) , fibroblast growth factor receptor 1 , cancer research , adenocarcinoma , biology , cell , basal (medicine) , lung , lung cancer , cell growth , receptor , fibroblast growth factor , medicine , cancer , endocrinology , genetics , paleontology , insulin
Fibroblast growth factor receptor 1 (FGFR1) is frequently amplified in human small-cell lung cancer (SCLC), but its contribution to SCLC and other lung tumors has remained elusive. Here, we assess the tumorigenic capacity of constitutive-active FGFR1 (FGFR1 K656E ) with concomitant RB and P53 depletion in mouse lung. Our results reveal a context-dependent effect of FGFR1 K656E : it impairs SCLC development from CGRP POS neuroendocrine (NE) cells, which are considered the major cell of origin of SCLC, whereas it promotes SCLC and low-grade NE bronchial lesions from tracheobronchial-basal cells. Moreover, FGFR1 K656E induces lung adenocarcinoma (LADC) from most lung cell compartments. However, its expression is not sustained in LADC originating from CGRP POS cells. Therefore, cell context and tumor stage should be taken into account when considering FGFR1 inhibition as a therapeutic option.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom