Oncode Institute, Division of Molecular Genetics, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Division of Molecular Oncology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Cell Rep. 2020 Mar 17;30(11):3837-3850.e3. doi: 10.1016/j.celrep.2020.02.052.
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) with concomitant RB and P53 depletion in mouse lung. Our results reveal a context-dependent effect of FGFR1: it impairs SCLC development from CGRP 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 induces lung adenocarcinoma (LADC) from most lung cell compartments. However, its expression is not sustained in LADC originating from CGRP cells. Therefore, cell context and tumor stage should be taken into account when considering FGFR1 inhibition as a therapeutic option.
成纤维细胞生长因子受体 1（FGFR1）在人类小细胞肺癌（SCLC）中经常扩增，但它对 SCLC 和其他肺癌的贡献仍然难以捉摸。在这里，我们评估了在小鼠肺中同时耗尽 RB 和 P53 情况下组成性激活的 FGFR1（FGFR1）的致瘤能力。我们的结果揭示了 FGFR1 的一种依赖于背景的效应：它损害了 CGRP 神经内分泌（NE）细胞来源的 SCLC 的发展，这些细胞被认为是 SCLC 的主要起源细胞，而它促进了来自气管支气管-基底细胞的 SCLC 和低级别 NE 支气管病变。此外，FGFR1 诱导来自大多数肺细胞区室的肺腺癌（LADC）。然而，它在源自 CGRP 细胞的 LADC 中并不持续表达。因此，在考虑将 FGFR1 抑制作为一种治疗选择时，应该考虑细胞背景和肿瘤阶段。
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