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FGFR1 Oncogenic Activation Reveals an Alternative Cell of Origin of SCLC in Rb1/p53 Mice.

ABSTRACT: 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.

SUBMITTER: Ferone G

PROVIDER: S-EPMC7090386 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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FGFR1 Oncogenic Activation Reveals an Alternative Cell of Origin of SCLC in Rb1/p53 Mice.

Ferone Giustina G Song Ji-Ying JY Krijgsman Oscar O van der Vliet Jan J Cozijnsen Miranda M Semenova Ekaterina A EA Adams David J DJ Peeper Daniel D Berns Anton A

Cell reports 20200301 11

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 (FGFR1K656E) with concomitant RB and P53 depletion in mouse lung. Our results reveal a context-dependent effect of FGFR1K656E: it impairs SCLC development from CGRPPOS neuroendocrine (NE) cells, which are considered ...[more]

PMID: 32187553

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